Potassium—induced Contraction in Smooth Muscle

Japanese Journal of Smooth Muncle Research 20: 427-444, 1984

Potassium—induced Contraction in Smooth Muscle

Hideaki KARAKI, Norimoto URAKAWA and Phyllis KUTSKY*

Department of Veterinary Pharmacology, Faculty of Agriculture, The University of

Tokyo, Bunkyo-ku, Tokyo 113 Japan, and *Department of Physiology, Texas

College of Osteopathic Medicine, Fort Worth, Texas 76107 USA.

Summary

High K-induced contractions in the smooth muscle of rabbit aorta and guinea pig

taenia coli may be described as follows: High K depolarizes the smooth muscle cell

membrane and opens voltage dependent Ca channels, resulting in an influx of extracel-

lular Ca and an activation of contractile machinery. A part of the cellular Ca is taken

up by mitochondria. Oxygen consumption of the muscle increases to compensate for

the ATP consumed by contraction. Hyperosmotic high K solution induces osmotic

shrinkage of the cell which uncouples membrane excitation from contraction. Isos-

motic high K, Na deficient solution induces swelling of the cell and also inhibits the

synport of Na and glucose resulting in an ATP deficiency; both of the changes could

inhibit muscle contractile tension. Na deficiency may also stimulate Ca influx coupled

to N a efflux in some smooth muscle preparations although such mechanism does not

seem to play an important role in rabbit aorta and guinea pig taenia coli.

Introduction

It has been established that a physiological saline solution containing a high concentration

of potassium (high K solution) depolarizes the plasma membrane of excitable cells and induces

contraction in skeletal (Frank, 1960), cardiac (Niedergerke, 1956) and smooth muscles

(Edman & Schild, 1962). In smooth muscle preparations, the high K-induced contraction is

widely employed to study excitation-contraction coupling and is also utilized as a standard

contraction for the evaluation of various smooth muscle relaxants (Weiss, 1975, 1977). High K

solution is usually made either by adding KC1 hyperosmotically to a physiological solution

(hyperosmotic high K solution) or by substituting an appropriate amount of Na in the physiolog-ical solution by equimolar K (isosmotic high K, low Na solution). Although, these two

solutions differ considerably in their N a concentration and tonicity, and consequently affect

smooth muscle function differently, little attention has been accumulated on these differences

(e. g., see Karaki et al., 1981a). In this review, the changes induced by hyperosmotic and

isosmotic high K solutions in membrane potential, contraction, water content, metabolism and

Ca movement are compared in two of the most widely used smooth muscle preparations, rabbit

Accepted for publication September 18, 1984.Reprint requests, Hedeaki, Karaki, Department of Veterinary Pharmacology , Faculty of Agriculture, TheUniversity of Tokyo, Bunkyo-ku, Tokyo 113, Japan.

428 H. KARAKI, N. URAKAWA and P. KUTSKY

thoracic aorta and guinea pig taenia coli.

Membrane potential

Increasing the external K concentration decreases the membrane potential according to the

Nernst or Goldman equation, and this K-induced depolarization is not affected by changes in

the Na concentration in the medium in rabbit aorta (Mekata, 1976) and taenia coli (Holman,

1958). Membrane depolarization induced by K salts with less permeable anions (K2 SO4 or

K-C2 H5SO3) is larger than that induced by KC1, while a more permeable salt, KNO3, induces

less depolarization than KC1 (Burnstock et al., 1963; Kuriyama, 1963). In rabbit aorta, an

increase in external K concentration induces only a graded depolarization (Mekata, 1976). In

taenia coli, as well as in other spike-generating smooth muscles like uterus, vas deferens and

ureter, an increase in the external K concentration induces a burst of spike discharges followed

by a spike-free membrane depolarization (Burnstock et al., 1963; Shimo & Holland, 1966 ;

Bolton, 1972; Johnishi & Sunano, 1978). In guinea pig portal vein, a hyperosmotic solution

itself depolarizes the membrane (Kuriyama et al., 1971).

Besides the depolarizing effect, high K solutions show an effect to hyperpolarize the smooth

muscle membrane. This effect is clearly seen in the smooth muscle preincubated with low K

solutions. The K-induced hyperpolarization is transient and is usually followed by muscle

relaxation. This hyperpolarization is attributable to stimulation of electrogenic Na pump

(Kuriyama et al., 1971; Bonaccorsi et al., 1977) and also to increase in K permeability (Somlyo

et al., 1972).

Muscle tension

Isotonic and isometric contractions

Smooth muscle contraction is recorded either isotonically using a lever, or isometrically

using a force transducer. In an isotonic recording, especially with a light load, muscle relaxa-

tion is sometimes obscured. In isometric recording, high-K induced contraction in taenia coli

relaxes to approximately 10% of the control contraction when a hypoxic condition is

introduced, and the remaining contraction is abolished when the muscle is washed with a

normal physiological solution. However, such a hypoxia-induced relaxation of K-induced

contraction is not seen in isotonic recording with a light load. Moreover, no relaxation is

observed when the high K-contracted taenia is washed with a normal physiological solution

under hypoxia. This"catch-like" contraction continues until oxygen is re-introduced

(Ishida & Urakawa, 1974). In taenia, a high concentration of ouabain relaxes the K-induced

contraction in isometric recording, but not in isotonic recording with a light load (unpublished

observation). In guinea pig vas deferens, it is also observed that the high K-induced initial

contraction is much larger than the following sustained contraction in isometric recording,

although both contractions have comparable magnitude in isotonic recording (Sunano &

Shimodan, 1981). By increasing the load on the isotonic recording lever, the results obtained

with this method became similar to those obtained with the isometric recording method

(Ishida & Urakawa, 1974).

Initial transient and following sustained contractions

K-contraction in smooth muscle 429

In guinea pig taenia coli, contractions induced by high K solutions (either hyperosmotic or

isosmotic), are rapidly inhibited in a Ca depleted solution (Chujyo & Holland, 1963; Karaki et

al., 1966). However, there are some data indicating differences between the initial transient

and the following sustained contractions in taenia coli. Substitution of Cl by other anions like

Br, NO3, I or SCN potentiates the K-induced initial transient contraction, whereas the same

substitution inhibits the following sustained contraction (Urakawa et al., 1967). Only an initial

transient contraction is induced by high K (and also by carbachol) in the presence of Ca

antagonists like verapamil (Riemer et al., 1974; Karaki et al., 1984), D600 (Brading & Sneddon,

1980), ruthenium red (Kawamura & Yabu, 1978), cyproheptadine (Lowe et al., 1981) and N2-

dansyl-L-arginine-4-t-butylpiperidine amide (TI 233) (Karaki et al., 1983c), inhibitors of

aerobic metabolism (Pfaffman et al., 1965; Ferrari & Carpenedo, 1968 ; Tsuda et al., 1977;

Nakagawa et al., 1984), inhibitors of the Na pump like ouabain (Pfaffman et al., 1965;

Kishimoto & Urakawa, 1982a), Li substitution for Na (Pfaffman et al., 1965; Kishimoto &

Urakawa, 1982a), and ionophores with mitochondrial inhibiting action like monensin (Ki-

shimoto et al., 1982) and X-537A (Ishida & Shibata, 1982; Murakami et al., 1983). The initial

transient contraction induced by high K in taenia coli coinsides with a burst of spike discharges

(Shimo & Holland, 1966). This electrical change, as well as initial transient contraction, is

relatively insensitive to the inhibitory effects of Mn (Brading et al., 1969) and D600 (Inomata &

Kao, 1976). These results indicate that the sustained contraction induced by high K (and also

by carbachol) in taenia coli may be dependent on Na pump activity, aerobic metabolism and Ca

influx through a pathway which is sensitive to Ca antagonists. In contrast, the initial transient

contraction may be due to different mechanisms.

There are two conflicting reports on the source of Ca for the initial transient contraction

induced by high K solution. Urakawa and Holland (1964) reported that this contraction is

attributable to a release of cellular Ca, while Imai and Takeda (1967) suggested this contraction

to be a result of Ca influx. Ca free, EGTA-containing solutions inhibit the contraction induced

not only by high K but also by carbachol at 37•Ž. However, initial transient contraction

induced by carbachol is likely to be due to release of cellular Ca (which is lost rapidly at 37•Ž)

because carbachol induces a transient contraction in Ca-free, high K solution at 20•Ž, which is

not inhibited by either verapamil or La (Ohashi et al., 1974, 1975). Since these experiments

were done in high K solutions, high K does not seem to release the carbachol-releasable Ca

store. Thus, although there are many similarlities in the transient contractions induced by

either high K or carbachol, Ca movements responsible for these contractions may differ.

In rabbit aorta, K-induced contraction is rapidly inhibited by removing external Ca , whereas norepinephrine-induced contraction is not readily inhibited in a Ca-deficient solution

(Waugh, 1962; Hudgins & Weiss, 1968). Addition of EGTA or lanthanum inhibits the sus-

tained contraction, but not the initial transient contraction induced by norepinephrine (Van

Breemen, 1969; Karaki et al., 1979). Thus, in rabbit aorta, K-induced contraction is composed,

of a single, sustained contraction which seems to be the result of Ca influx, whereas norepine-

phrine-induced contraction is composed of an initial transient and a following sustained


contraction; the former seems to be the result of Ca release while the latter may be the result

of inward dislocation of superficially bound Ca (Karaki et al., 1979; Karaki, 1981 ; Karaki &

Weiss, 1984; Karaki et al., 1984). Sodium nitroprusside and procaine inhibits both of the

norepinephrine-induced Ca movements in aorta (unpublished observation).

Hyperosmotic high K solution

Effects of hyperosmotic high K solution on muscle tension in rabbit aorta and guinea pig

taenia coli are shown in Fig. 1. In both aorta and taenia coli, hyperosmotic application of KC1

initiates a contraction when the K concentration is 15 to 20 mM and the contraction reaches a

maximum when 40 to 50 mM KC1 is added. Further increase in the KC1 concentration, up to

160 mM, does not change the contractile tension in aorta. In taenia coli, however, a concentra-

tion-dependent decrease in developed tension is observed when the concentration of KC1 is

above 80 mM (Karaki et al. 1983a). In taenia coli, the hyperosmotic high K solution does not

induce contraction in the absence of Ca or in the presence of verapamil. In aorta, however, the

hyperosmotic high K solution induces a concentration-dependent contraction even in the

absence of Ca or in the presence of verapamil. The threshold concentration of K to induce

contraction in aorta in Ca-depleted solution is 40 mM and when 80 mM KC1 is added, a muscle

contraction of more than 50% of that induced in the presence of 1.5 mM Ca is induced.

Hyperosmotic application of NaCl or sucrose also induces a concentration-dependent contrac-

tion in aorta which is not inhibited by Ca removal, verapamil, papaverine or sodium nitroprus-

side. The contraction is rapidly relaxed by washing the muscle with normal physiological

solution and norepinephrine applied thereafter induces a contraction similar to that of control

muscle (Karaki et al., 1983a). In canine femoral, superior mesenteric and coronary arteries,

hyperosmotic application of sucrose or mannitol also induces concentration-dependent contrac-

tions, and these contractions are not inhibited by Ca removal or addition of Ca antagonists like

verapamil, nicardipine and diltiazem, but are partially inhibited by papaverine, 2,4-dinitro-

phenol or chlorpromazine (Nakayama & Kato, 1980). In rat portal vein, hyperosmotic su-

crose-induced contraction is not inhibited by Ca removal, but is partially inhibited by a glucose-

and oxygen-deprivation (Andersson et al., 1974). In rat aorta, hyperosmotic sucrose-induced

contraction is not inhibited by verapamil and is partially inhibited by Ca-removal and by

papaverine (Kent et al., 1983). Another effect of hyperosmotic solution is to inhibit the

excitation-contraction coupling (Brading, 1970; Somlyo & Somlyo, 1970); the effects of

various agonists, like norepinephrine and histamine, to induce smooth muscle contractions are

inhibited in hyperosmotic solution although the effects on membrane potential are not altered

(Carrol, 1969; Somlyo & Somlyo, 1970; Krishnamurty et al., 1977; Kent et al., 1983). In both

aorta and taenia coli, a portion of high K-induced contraction which is dependent on external

Ca is inhibited when the osmolarity of the medium is increased (Fig. 1).

Isosmotic high K, low Na solution

Effects of isosmotic high K, low N a solution on muscle tension in rabbit aorta and guinea

pig taenia coli are shown in Fig. 1. In both aorta and taenia coli, isosmotic application of KCl

induces a contraction; a maximum is reached when 40 to 50 mM KCl was applied. Further


Hyperosmotically added K (mM)

Isosmotically substituted K (mM)

Fig. 1. Steady level of muscle tension induced by hyperosmotically added K (upperand middle) and isosmotically substituted K (lower) in rabbit aorta and guinea pig taenia coli in the presence or

absence of external Ca. Steady contractile tension was reached between 15 to 120 min after the addition of high K depending on the concentration of N a and K.

increase in the concentration of K (and decrease in the concentration of Na) does not change

the maximum tension level reached soon after the addition of high K solution. However, the

sustained contractile tension in aorta is inhibited when the concentration of K is higher than 120

mM (Suzuki et al., 1981; Karaki et al., 1982b). In taenia coli, isosmotic application of 60 mM

or higher KC1 induces a rapid rise in tension followed by a slow decrease; the rate of decrease

in tension correlates with the increase in K concentration (or the decrease in Na concentration)

of the isosmotic high K, low Na solutions (Urakawa et al., 1968; Karaki et al., 1969a;

Sunano & Shimodan, 1981). A similar decrease in the sustained tension level is observed

during contraction induced by isosmotic high K solution in rabbit trachea (Ueda et al., 1982),

guinea pig trachea, urinary bladder and gall bladder (Shimizu et al., 1984). In isotonic record-


ing with a light load, however, the decrease in the sustained contractile tensionis rarely seen

(unpublished observation). The muscle contraction induced by isosmotic high K solution in rabbit aorta and guinea pig

taenia coli is totally inhibited in a solution without Ca or by verapamil (Karaki et al., 1983a).

In guinea pig aorta, however, a part of the contraction induced by isosmotic high K, Na

deficient (11.9 mM) solution is not inhibited by verapamil (Ozaki & Urakawa, 1981a). In this

smooth muscle preparation, a sustained contraction is induced by a decrease in transmembrane

Na gradient, produced either by inhibiting the Na pump (using ouabain or a K deficient solution)

or by decreasing the concentration of external Na. This contraction is not inhibited by

verapamil and is possibly due to an influx of Ca in exchange for Na efflux (Ozaki & Urakawa , 1979, 1980, 1981a, b; Ozaki et al., 1978). Thus, it is possible that a part of the contraction

induced by high K, N a deficient solution in guinea pig aorta is a result of Na-Ca exchange.

Such a N a-Ca exchange mechanism, however, does not seem to play an important role in rabbit

aorta and guinea pig taenia coli (Karaki & Urakawa, 1977; Karaki et al., 1978a; Ozaki &

Urakawa, 1981b; Van Breemen et al., 1979, 1980).

Tris buffer is sometimes substituted for bicarbonate buffer. Recently, it has been suggest-

ed that Tris and other artificial buffer substances inhibit smooth muscle contractions, especially

those induced by isosmotic high K solution (Altura et al., 1980 ; Turlapaty et al., 1978 , 1979a, b). However, the inhibition observed in the artificial buffer solution is not attributable to the

adverse effects of the buffer substances, but to an inadequate method of adjusting the medium

pH and to a Na deficiency of the medium due to replacement of NaHCO3 with Tris (Karaki &

Weiss, 1981b; Karaki et al., 1981a, b).

Cell water content

In skeletal muscle, membrane permeability to Na is much smaller than to K and Cl and the

distribution of K and Cl in and outside the cell is described by a Donnan equation:

Kout/ Kin= Clin/ Clout

where Kout and Kin represent K ion concentration outside and inside, respectively, of the cell

membrane, and Clout and Clin represent Cl ion concentration outside and inside, respectively, of

the cell membrane. When external Na is substituted by K, the increase in Kout is followed by

an increase in Kin and also Clin. Such a change in ionic distribution results in a large increase

in wet weight of the tissue due to an influx of water and swelling of the cell (Boyle & Conway , 1941; MacKnight & Leaf, 1977). In smooth muscle, however, an increase in wet weight in

isosmotic high K, low N a solution is not observed (Casteels & Kuriyama, 1966; Brading &

Tomita, 1968). The discrepancy between skeletal and smooth muscle is explained by measur-

ing the changes in the extracellular space. In smooth muscle, isosmotic high K, N a deficient

solution increases cell water content and simultaneously decreases extracellular space and thus

maintains the wet weight of the tissue constant within 30 min of the application of isosmotic

high K solution (Jones et al., 1973). The rate of swelling is slow in smooth muscle cells; it

takes more than 60 min to obtain a significant increase in the wet weight in isosmotic high K,

Na daficient solution (Jones et al., 1973; Karaki et al., 1978b ; Suzuki et al., 1980, 1981).

In rabbit aorta, the time courses for the decrease in the sustained contraction and the


increase in the cell water content induced in isosmotic high K (120 mM or higher), N a deficient

solution are almost identical (Suzuki et al., 1981). When the external NaCl is substituted by

a K salt with a highly permeable anion, like KI or KNO3 both the decrease in the sustained

contraction and cell swelling take place more rapidly than in KC1 solution. However, when

NaCl is substituted by a K salt of a practically impermeable anion, like K2SO4 or K propionate,

there is little change in either the sustained contraction or the cell water content. Hyperos-

motic addition of 50 to 100 mM sucrose completely prevents both of these changes in the

isosmotic high K, Na deficient solution (Suzuki et al., 1981). Similar phenomena are found in

rabbit trachea (Ueda et al., 1983), guinea pig trachea and gall bladder (Shimizu et al., 1984).

Thus, it seems likely that swelling of the smooth muscle cell somehow inhibits K-induced

contraction in rabbit aorta and other smooth muscles.

In guinea pig taenia coli, the increase in the cell water content in the isosmotic KC1 solution

is also prevented by the application of hyperosmotic sucrose. However, the decrease in the

sustained contractile tension is only partly prevented by sucrose (Suzuki et al., 1980). Similar

results are obtained in guinea pig urinary bladder (Shimizu et al., 1984). As described in the

following section, the Na deficiency in the isosmotic high K solution may inhibit glucose uptake

of the cell and decrease ATP synthesis, thus inhibiting contraction in taenia coli.

The differential effects of hyperosmotic high K and isosmotic high K solutions on smooth

muscle contraction are summarized in Fig. 2.

Metabolism

Oxygen consumption of taenia coli, 0.43-0.62 ƒÊmol/g/min (Bulbring, 1953; Billbring &

Golenhofen, 1967 ; Saito et al., 1968; Karaki et al., 1982b), is higher than that of aorta, 0.075-

0.14 ƒÊmol/g/min (Paul, 1980; Karaki et al., 1982b). In the presence of 40 to 80 mM K, oxygen

consumption of both tissues increases to 150-280% of the resting level (Saito et al., 1968; Paul,

1980; Karaki et al., 1982b). The ATP content of taenia coli and of aorta are 2 ƒÊmol/g and 0.7

Fig. 2. Differential effects of hyperosmotically added K and isosmotically substituted

K on the smooth muscle contraction.


ƒÊ mol/g, respectively, and 40 to 80 mM K does not change or slightly decreases this (Paul, 1980;

Karaki et al., 1982b). Under hypoxic conditions, the ATP content of resting muscle does not

change, whereas on the addition of K the ATP content rapidly decreases (Karaki et al., 1982b).

Therefere, it seems likely that ATP production increases by an aerobic pathway to replenish

ATP consumed during K-induced contration.

In taenia coli, prolonged exposure of the muscle to isosmotic high K, Na deficient solution

gradually decreases the sustained contractile tension. When the sustained contraction

decreases to 20% or 10% of the maximum contraction, oxygen consumption of the muscle also

decreases to 18% or 0%, respectively, of the maximum level. ATP content also decreases

during this period. Similar changes are seen when glucose is removed from the medium during

the contraction induced by a hyperosmotic high K solution. Addition of 50 mM NaCl or 5.5

mM pyruvate to isosmotic high K, Na deficient solution increases the muscle tension, oxygen

consumption and ATP content (Karaki et al., 1982b). These results suggest that co-transport

of Na and glucose (Schultz & Curran, 1970) is inhibited in the isosmotic high K, Na deficient

solution resulting in a decrease in ATP synthesis. Hypoxia also decreases K-induced contrac-

tile tension in taenia coli (Pfaffman et al., 1965; Karaki et al., 1967; Ganeshanandan et al.,

1969). Increasing the concentration of glucose to 25 mM or higher under hypoxia partially

restores the muscle tession in the presence of Na (Namm & Zucker, 1973; Nasu et al., 1982).

The decrease in ATP content under hypoxia is also partially prevented by increasing the

glucose concentration (Karaki et al., 1982b; Ishida et al. 1984). Thus, a part of the ATP utilized for muscle contraction seems to be synthesized by an anaerobic glycolytic pathway .

In rabbit aorta, neither glucose removal nor hypoxia inhibits the K-induced contractile

tesion. ATP content does not change during the K-induced contraction under hypoxia (Karaki

et al., 1982b). However, both oxygen consumption and ATP content decrease to 32% and 66%,

respectively, of the control levels during K-induced contraction in glucose depleted solution

(Karaki et al., 1982b). Since aorta is able to utilize endogenous amino acids and fatty acid as metabolic substrates (Hellstrand et al., 1977; Chase & Odessey, 1981), muscle contractions may

be maintained by these substrates in the absence of added glucose. In isosmotic high K, Na

deficient solution, both oxygen consumption and ATP content decrease to levels similar to

those in glucose-depleted, hyperosmotic high-K solution (Karaki et al., 1982b). These

decreases are not prevented even in the presence of hyperosmotically applied sucrose, which

inhibites both cell swelling and tension decrease in isosmotic high K, Na deficient solution,

suggesting that cell swelling does not affect metabolism in aorta. From these results, it seems

likely that, in aorta as in taenia coli, glucose uptake is inhibited in aorta in isosmotic high K,

Na deficient solution. However, endogenous substrates may partly support ATP synthesis and

maintain the K-induced contraction in aorta. On the other hand, norepinephrine-induced

contraction in rabbit aorta is inhibited by either glucose depletion or hypoxia. However, this

contraction is not inhibited by cell swelling induced by decreasing the Na concentration to 1/2

of the normal solution without any osmotic substitution (unpublished observation). These

results suggest a difference in the excitation-contraction coupling processes in K-versus

norepinephrine-induced contractions.


Calcium movements

Tissue Ca content

Tissue Ca content (total tissue Ca content measured by flame photometry or atomic

absorption spectrometry) of taenia coli increases during a contraction induced by hyperosmotic

42.7 mM K solution (Urakawa & Holland, 1964; Karaki et al., 1969b). Such an increase is not

observed during a contraction induced by isosmotic high K, Na deficient solutions (Urakawa et

al., 1968; Karaki et al., 1969a), histamine (Nasu et al., 1971), barium (Karaki et al., 1969b) or

acetylcholine (Nasu & Urakawa, 1973). In rabbit aorta, tissue Ca content is not affected by

high K solutions (either isosmotic or hyperosmotic), or by norepinephrine (unpublished observa-

tions).

Slowly exchangeable 45Ca fraction

In taenia coli, it is found that smooth muscle stimulants including high K, carbachol,

histamine and Ba increase the amount of 45Ca bound to relatively slowly exchangeable sites

(t 1/2=7 min) possibly located on the membrane surface. Changes in the size of this fraction

show a good correlation with changes in muscle tension and this fraction has been suggested to

be a depot of Ca extruded from the cell during muscle contraction (Karaki & Urakawa, 1972).

A similar 45Ca fraction is found to be increase by high K solution in rabbit aorta (Briggs, 1962).

Ouabain also increases this Ca fraction (Briggs & Shibata, 1966) which is due to the effect of

endogenous catecholamines released by ouabain (Karaki & Urakawa, 1977; Karaki et al.,

1978a).

Cellular 45Ca fraction and the rate of 45Ca uptake

A lanthanum-wash method (Van Breemen & McNaughton, 1970; Van Breemen et al.,

1972) is widely employed to displace extracellular 45Ca and thus enable determination of the

amount of cellular 45Ca in smooth muscle. It has been shown that the cellular 45Ca (total

amount of cellular exchangeable Ca) of smooth muscle, measured by equilibrating the muscle

with 45Ca for more than 30 min, is increased by high K solutions (for references see Karaki et

al., 1982a). In rabbit aorta, isosmotic 20 mM or higher K increases the cellular 45Ca in a

concentration-dependent manner and when all the Na in the medium is replaced by K, cellular

45Ca increases 300-800 nmol/g above the resting level (Van Breemen, 1977; Karaki & Weiss,

1979). Hyperosmotic high K solutions also increase the cellular 45Ca in a concentration-

dependent manner (Ito et al., 1977). This increase in cellular 45Ca is attributable to the influx

of Ca through voltage dependent Ca channels since this increment is specifically inhibited by

verapamil (Ito et al., 1977; Karaki & Weiss, 1979; Karaki et al., 1982a). The increased

cellular 45Ca seems to be located mainly in mitochondria because mitochondrial inhibitors like

antimycin A, oligomycin, KCN or hypoxia inhibit the increase in cellular 45Ca (Karaki & Weiss,

1981a; Karaki et al., 1982a). The K-induced contraction, on the other hand, is not inhibited

by the mitochondrial inhibitors, suggesting that the Ca accumulation by mitochondria does not

play an important role in muscle contraction (Karaki & Weiss, 1981a; Karaki et al., 1982a). Although a high concentration of K does not increase the total 45Ca content under hypoxia, it


increases the rate of 45Ca uptake (Karaki et al., 1983b) measured by a short (less than 10 min)

45Ca-incubation period (pulse-label method) (Kroeger et al., 1975). This increase in the rate of

45Ca uptake is inhibited by verapamil (Karaki et al., 1984). Thus, a high concentration of K has

dual effects on Ca movements in rabbit aorta, to increase the rate of 45Ca uptake and to

accumulate 45Ca in mitochondria. The latter 45Ca is detected as increase in cellular 45Ca

content. Similar results have been obtained in the intestinal smooth muscle of guinea pig

taenia coli (Karaki et al., 1982a, 1984).

An increase in the total cellular 45Ca has been found only when the plasma membrane of

rabbit aorta is depolarized. Other stimulants, such as norepinephrine, histamine and angioten-

sin II, do not change the cellular 45Ca in rabbit aorta (Deth & Van Breemen, 1974). Further-

more, the norepinephrine-induced contraction in rabbit aorta is relatively insensitive to ver-

apamil and other organic Ca antagonists (Kalsner et al., 1970; Schumann et al., 1975;

Golenhofen & Weston, 1976; Ito et al., 1977; Van Breemen et al., 1981). From these results,

it is sometimes concluded that norepinephrine-induced contraction is not dependent on external

Ca. However, norepinephrine or histamine, added to an aorta depolarized by isosmotic high

K, Na deficient solution, induces a further increase in cellular 45Ca (Karaki & Weiss, 1979, 1980)

although, when the concentration of K is lower than 120 mM, norepinephrine does not show an

additive increase in cellular 45Ca (unpublished observation). Such an additive increase in

cellular "Ca may be attributable to the accumulation of 45Ca by mitochondria since the

increment is inhibited by mitochondrial inhibitors (unpublished observation). Norepinephrine

also increases the rate of 45Ca uptake (Godfraind, 1976; Karaki et al., 1983b). This increase

in the rate of 45Ca uptake is detected by a modified lanthanum-wash method using a high

concentration (50-80.8 mM) of La and/or low temperature (Godfraind, 1976 ; Karaki et al.,

1983b), but is not detected by the original lanthanum-wash method using 2 to 10 mM La and

37•Ž (Van Breemen & McNaughton, 1970 ; Van Breemen et al., 1972). Washing the 45Ca-

treated muscle with EGTA at low temperature seems to remove extracellular bound 45Ca in a

manner similar to the modified lanthanum-wash method (Meisheri et al., 1981). Such an

increase in the rate of 45Ca uptake is inhibited by neither mitochondrial inhibitors (Karaki &

Weiss, 1985) nor by verapamil (Karaki et al., 1984). These results suggest that the sustained

contraction induced by norepinephrine is due to an influx of Ca through a Ca channel which is

insensitive to verapamil, and that this Ca is not accumulated in the cell (or mitochondria) during

the norepinephrine-induced contraction of polarized rabbit aorta.

Ca movements in rabbit aorta during contraction induced by high K and norepinephrine are

summarized in Fig. 3.

Calcium channels

Organic Ca antagonists are specific inhibitors of K-induced contraction in smooth muscle.

The increases in both the amount of cellular Ca and the rate of Ca exchange induced by high

K solution are inhibited by verapamil or D600 in rabbit aorta (Van Breemen et al., 1972; Ito

et al., 1977; Karaki & Weiss, 1979; Thorens & Haeusler, 1979; Meisheri et al., 1981; Karaki

et al., 1982b). On the other hand, verapamil or D600 has little effect on the norepinephrine-

induced Ca movements in rabbit aorta (Karaki & Weiss, 1980; Meisheri et al., 1981; Karaki

437

Fig. 3. Ca movements in rabbit aorta. High K depolarizes cell membrane and opens a voltage-

dependent Ca channel which is inhibited by verapamil. High K also increases mitochondrial Ca uptake which is inhibited by hypoxia. Following the norepinephrine-receptor interaction,

Ca bound to the membrane surface is taken up through receptor-linked channel. Cellular

bound Ca is also released. Both of the norepinephrine-induced Ca movements are inhibited by

sodium nitroprusside whereas Ca release is inhibited by procaine. Ca in the cell is extruded and

binds to the membrane surface. Open arrows; stimulation. Filled arrows; inhibition.

et al., 1984). The latter changes in Ca movements are inhibited by sodium nitroprusside

(Karaki & Weiss, 1980; Karaki et al., 1984). These results support the suggestion that there

are two types of Ca channels in smooth muscle, i.e., a voltage-dependent Ca channel and a

receptor-linked Ca channel (Weiss, 1977, 1981; Bolton, 1979; Van Breemen et al., 1979;

Triggle, 1981). Furthermore, it seems quite likely that the organic Ca antagonists and sodium

nitroprusside are specific inhibitors of the respective channels in rabbit aorta (see also Golen-

hofen, 1981). Although there seems to be two types of Ca channels in other types of smooth

muscle, such a relationship between Ca channels and specific inhibitors is seen only in rabbit

aorta. In most other vascular smooth muscles, K-induced contraction is inhibited by both

verapamil and sodium nitroprusside while norepinephrine-induced contraction is also inhibited

by both verapamil and sodium nitroprusside (Karaki & Weiss, 1984; Karaki et al., 1984).

Therefore, voltage-dependent Ca channels and receptor-linked Ca channels in these smooth

muscles seem to have common characteristics, or these two Ca channels are not functionally

separated. In guinea pig taenia coli (and other intestinal smooth muscles), organic Ca antago-

nists inhibit both the sustained contraction and the Ca movements induced by high K solution

and by histamine, while sodium nitroprusside has little effect on these changes (Karaki et al.,

1984). Thus, taenia coli does not seem to have a Ca channel which is inhibited by sodium

nitroprusside (for further details see Karaki & Weiss, 1984; Karaki et al., 1984).

Accumulation of Na in the cell, induced by ouabain or vanadate, is reported to inhibit the


voltage-dependent Ca channel (Kishimoto & Urakawa, 1982a; Kishimoto et al., 1980; Ueda et

al., 1982).Intracellular Li may have a similar but more potent effect than intracellular Na

(Kishimoto & Urakawa, 1982b). In contrast, bassianolide, a cyclodepsipeptide, inhibits the

sustained contractions induced by various receptor-agonists (i.e., acetylcholine, histamine,

serotonin and norepinephrine) whereas this inhibitor has no effect on the contraction induced by

high K solution in guinea pig taenia coli, ileum and was deferens (Nakajo et al., 1982, 1983).

These findings further support the concept of different pathways of Ca influx in the contraction

induced by a high concentration of K and by receptor-agonists.

References

Altura, B.M., Altura, B.T., Carella, A. & Turlapaty, P.D.M.V. (1980). Adverse effects of artificial

buffers on contractile responses of arterial and venous smooth muscle. Br. J. Pharmacol. 69:

207-214.

Andersson, C., Hellstrand, K. Johansson, B. & Ringberg, A. (1974). Contraction in venous smooth

muscle induced by hypertonicity. Calcium dependence and mechanical characteristics.

Acta Physiol. Scand. 90: 451-461.

Bolton, T.B. (1972). The depolarizing action of acetylcholine or carbachol in intestinal smooth

muscle. J. Physiol. 216: 404-418.

Bolton, T.B. (1979). Mechanism of actions of neurotransmitters and other substances on smooth

muscle. Physiol. Rev. 59: 606-718.

Bonaccorsi, A., Hermsmeyer, K., Aprigliano, O., Smith, C.B. & Bohr, D.F. (1977). Mechanism of

potassium relaxation of arterial muscle. Blood Vessels 14 : 261-276.Boyle, F.C. & Conway, E. J. (1941). Potassium accumulation in muscle and associated changes. J.

Physiol. 100: 1-63.

Brading, A.F. (1970). Osmotic phenomena in smooth muscle. In: Smooth muscle, Edited by Bulbr-

ing, E., Brading, A.F., Jones, A.W. & Tomita, T., pp.166-196, Edward Arnold Ltd., London.

Brading, A.F. & Sneddon, P. (1980). Evidence for multiple source of calcium for activation of the

contractile mechanism of guinea-pig taenia coli on stimulation with carbachol. Br. J.

Pharmacol. 70: 229-240.

Brading, A.F. & Tomita, T. (1968). Effects of anions on the volume of smooth muscle. Nature,

London. 218: 276-277.

Brading, A.F., Bulbring, E. & Tomita, T. (1969). The effect of sodium and calcium on the action

potential of the smooth muscle of the guinea-pig taenia coli. J. Physiol. 200: 637-654.Briggs, A.H. (1962). Calcium movements during potassium contracture in isolated rabbit aortic strip.

Am. J. Physiol. 203: 849-852.

Briggs, A.H. & Shibata, S. (1966). Ca and ouabain intercation on vascular smooth muscle. Proc.

Soc. Exp. Biol. Med. 121: 274-278.

Bulbring, E. (1953). Measurements of oxygen consumption in smooth muscle. J. Physiol. 122: 111-

134.

Btilbring, E. & Golenhoffen, G. (1967). Oxygen consumption by the isolated smooth muscle of guinea-

pig taenia coli. J. Physiol. 193: 213-224.Burnstock, G., Holman, M.E. & Prosser, C.L. (1963). Electrophysiology of smooth muscle. Physiol.

Rev. 43: 482-527.

Carrol, P.M. (1969). The efect of hypertonic solution on the wet weight and contractions of rat uterus

and was deferens. J. gen. Physiol. 53: 590-607.

Casteels, R. & Kuriyama, H. (1966). Membrane potential and ion content in the smooth muscle of the

guinea-pig's taenia coli at different external potassium concentration. J. Physiol. 184: 120-


130.

Chase, K.V. & Odessey, R.L. (1981). The utilization by rabbit aorta of carbohydrates, fatty acids, ketone bodies and amino acids as substrates for energy production. Circulation Res. 48:

850-858.

Chujyo, N. & Holland, W.C. (1963). Potassium-induced contracture and calcium exchange in the

guinea pig's taenia coli. Am. J. Physiol. 205: 94-100.Deth, R. & Van Breemen, C. (1974). Relative contribution of Ca2+ influx and Ca2+ release during drug

induced contraction of the rabbit aorta. Pfliigers Arch. 348: 13-22.

Edman, K.A.P. & Schild, H.O. (1962). The need for calcium in the contractile responses induced by

acetylcholine and potassium in rat uterus. J. Physiol. 161: 424-441.

Ferrari, M. & Carpenedo, F. (1968). On the mechanism of action of some myolytic agents on

depolarized guinea pig taenia coli. Arch. Int. Pharmacodyn. 174: 223-228.

Frank, G.B. (1960). Effects of changes in extracellular calcium concentration on the potassium

induced contracture of frog's skeletal muscle. J. Physiol. 151: 518-538.

Ganeshanandan, S.S., Karaki, H., Ikeda, M. & Urakawa, N. (1969). Mechanical response of guinea

pig taenia coli in high-K/Na-deficient medium under anoxia. Jpn. J. Pharmacol. 19: 239-240.

Godfraind, T. (1976). Calcium exchange in vascular smooth muscle, action of noradrenaline and

lanthanum. J. Physiol. 260: 21-35.

Golenhofen, K. (1981). Differentiation of calcium activation process in smooth muscle using selective

antagonists. In: Smooth muscle, an assesment of current knowledge. Edited by Bulbring,

E., Jones, A.W. & Tomita, T. pp. 157-170, Edward Arnold, London.

Golenhofen, K. & Weston, A.H. (1976). Differentiation of calcium activation systems in vascular

smooth muscle. In: Ionic action on vascular smooth muscle. Edited by Betz, E. pp. 21-25,

Springer Verlag, Berlin.

Hellstrand, P., Johansson, B. & Norberg, K. (1977). Mechanical, electrical and biological effects of

hypoxia and substrate removal on spontaneously active vascular smooth muscle. Acta

Physiol. Scand. 100: 69-83.

Holman, M.E. (1958). Membrane potentials recorded with high-resistance microelectrodes and the

effects of changes in ionic environment on the electrical and mechanical activity of the

smooth muscle of the taenia coli of guinea pig. J. Physiol. 141: 464-488.

Hudgins, P.M. & Weiss, G.B. (1968). Differential effects of calcium removal upon vascular smooth

muscle contraction induced by norepinephrine, histamine and potassium, J. Pharmacol. Exp.

Ther. 159: 91-97.

Imai, S. & Takeda, K. (1967). Actions of calcium and certain multivalent cations on potassium

contracture of guinea-pig's taenia coli. J. Physiol. 190: 155-169.

Inomata, H. & Kao, C.Y. (1976). Ionic currents in the guinea-pig taenia coli. J. Physiol. 255: 347-

378.

Ishida. Y. & Shibata, S. (1982). Relaxing and metabolic inhibitory action of X537A (lasalocid) on the

taenia of the guinea-pig caecum. J. Physiol. 333: 293-304.

Ishida, Y. & Urakawa, N. (1974). Comparison between isometric and isotonic contractions in guinea-

pig taenia coli under anoxia. Jpn. J. Pharamcol. 24: 327-330. Ishida, Y., Takagi, K. & Urakawa, N. (1984). Tension maintenance, calcium content and energy

production of the taenia of the guinea-pig caecum under hypoxia. J. Physiol. 347: 149-159.Ito, K., Karaki, H. & Urakawa, N. (1977). The mode of contractile action of palytoxin on vascular

smooth muscle. Europ. J. Pharmacol. 46: 9-14.

Johnishi, J. & Sunano, S. (1978). The role of membrane electrical activities and extracellular calcium in high-K-induced contracture of guinea pig ureter. Jpn. J. Physiol. 28: 1-16.

Jones, A.W., Somlyo, A.P. & Somlyo, A.V. (1973). Potassium accmulation in smooth muscle and


associated ultrastructural changes. J. Physiol. 232: 247-273.

Kalsner, S., Nickerson, M. & Boyd, G.N. (1970). Selective blockade of potassium-induced contrac-

tions of aortic strips by ƒÀ-diethylaminoethyl diphenylpropylacetate (SKF 525A). J. Phar-

macol. Exp. Ther. 174: 500-508.

Karaki, H. (1981). Calcium components in vascular smooth muscle. Folia Pharmacol. Jpn. 77: 1-8.

Karaki, H. & Urakawa, N. (1972). A shift of cellular calcium to a more slowly exchangeable fraction

during contraction in guinea pig taenia coli. Jpn. J. Pharmacol. 22: 511-518.

Karaki, H. & Urakawa, N. (1977). Possible role of endogenous catecholamines in the contraction

induced in rabbit aorta by ouabain, sodium depletion and potassium depletion. Europ. J.

Pharmacol. 43: 65-72.

Karaki, H. & Weiss, G.B. (1979). Alterations in high and low affinity binding of 45Ca in rabbit aortic

smooth muscle by norepinephrine and potassium after exposure to lanthanum and low

temperature. J. Pharmacol. Exp. Ther. 211: 86-92.

Karaki, H. & Weiss, G.B. (1980). Effects of stimulatory agents on mobilization of high and low

affinity site 45Ca in rabbit aortic smooth muscle. J. Pharmacol. Exp. Ther. 213: 450-455.

Karaki, H. & Weiss, G.B. (1981a). Inhibitors of mitochondrial Ca *uptake dissociate potassium-

induced tension response from increased 45Ca retention in rabbit aortic smooth muscle.

Blood Vessels 18: 36-44.

Karaki, H. & Weiss, G.B. (1981b). Rabbit aortic contractile responses and 45Ca retention in tris and

bicarbonate buffers. Arch. Int. Pharmacodyn. 252: 29-39.

Karaki, H. & Weiss, G.B. (1984). Calcium channels in smooth muscle. Gastroenterology 87: 960-970.

Karaki, H. & Weiss, G.B. (1985). Modification by decreased temperature and hypoxia on 45Ca

movements in stimulated smooth muscle of rabbit aorta. Federation Proc. 44: (in press).

Karaki, H., Urakawa N. & Ikeda, M. (1966). Influences of external magnesium, bicarbonate and

phosphate on potassium-induced contracture of guinea pig taenia coli. Jpn. J. Pharmacol.

16: 423-437.

Karaki, H, Ikeda, M. & Urakawa, N. (1967). Effects of external calcium and some metabolic

inhibitors on barium-induced tension chasges in guinea pig taenia coli. Jpn. J. Pharmacol.

17: 603-612.

Karaki, H., Ganeshanandan, S.S., Ikeda, M. & Urakawa, N. (1969a). Changes in tension, Ca

movement and metabolism of guinea pig taenia coli in varying concentration of external Na

and K. Jpn. J. Pharmacol. 19: 569-577.

Karaki, H., Ikeda, M. & Urakawa, N. (1969b). Movement of calcium during tension development

induced by barium and high-potassium in guinea pig taenia coli. Jpn. J. Pharmacol. 19: 291-

299.

Karaki, H., Ozaki, H. & Urakawa, N. (1978a). Effects of ouabain and potassium-free solution on the

contraction of isolated blood vessels. Europ. J. Pharmacol. 48: 439-443.

Karaki, H., Suzuki, T. & Urakawa, N. (1978b). Changes in tissue weight and calcium content in

various high potassium solution in smooth muscle of guinea pig taenia coli. Jpn. J. Phar-

macol. 28: 633-636.

Karaki, H., Kubota, H. & Urakawa, N. (1979). Mobilization of stored calcium for phasic contraction

by norepinephrine in rabbit aorta. Europ. J. Pharmacol. 56 : 237-245.

Karaki, H., Suzuki, T. & Urakawa, N. (1981a). Tris does not inhibit isolated vascular or intestinal

smooth muscle contraction. Am. J. Physiol. 241 : H337-H341.

Karaki, H., Suzuki, T. & Urakawa, N. (1981b). Artificial buffers do not inhibit contractile responses

in the smooth muscle of rat portal vein and guinea pig taenia coli. Jpn. J. Pharmacol. 31:

979-983.

Karaki, H., Suzuki, T., Ozaki, H., Urakawa, N. & Ishida, Y. (1982a). Dissociation of K+-induced

tension and cellular Ca+ retention in vascular and intestinal smooth muscle in normoxia


and anoxia. Pfluger's Arch. 349: 118-123.

Karaki, H., Suzuki, T., Urakawa, N., Ishida, Y. & Shibata, S. (1982b). High K+, Na+-deficient

solution inhibits tension, O2 consumption, and ATP synthesis in smooth muscle. Jpn. J.

Pharmacol. 32: 727-733.

Karaki, H., Ahn, H.Y. & Urakawa, N. (1983a). Hyperosmotic applications of KCl induce vascular

smooth muscle contraction which is independent of external Ca. Jpn. J. Pharmacol. 33: 246-

248.

Karaki, H., Hatano, K. & Weiss, G.B. (1983b). Effects of magnesium on 45Ca uptake and release at

different sites in rabbit aortic smooth muscle. Pfluger's Arch. 398: 27-32.

Karaki, H., Murakami, K., Nakagawa, H. & Urakawa, N. (1983c). The inhibitory effect of N2-

dansyl-L-arginine-4-t-butylpiperidine amide (Tl 233) on vascular and intestinal smooth muscle contraction. Br. J. Pharmacol. 80: 519-525.

Karaki, H., Nakagawa, H. & Urakawa, N. (1984). Comparative effects of verapamil and sodium

nitroprusside on contraction and 45Ca uptake in the smooth muscle of rabbit aorta, rat aorta

and guinea pig taenia coli. Br. J. Pharmacol. 81: 393-400.

Kawamura, M. & Yabu, H. (1978). Selective inhibition of potassium contracture in guinea pig taenia

coli by ruthenium red. Jpn. J. Physiol. 28: 447-460.

Kent, R.L., Sheldon, R.J. & Harakal, C. (1983). The effects of hyperosmolar solutions on isolated

vascular smooth muscle examined with verapamil. Pharmacol. 26: 157-163.

Kishimoto, T. & Urakawa, N. (1982a). Effects of ouabain on high K-induced contractions of various

smooth muscle tissues in the guinea-pig. Jpn. J. Pharmacol. 32: 551-561.

Kishimoto, T. & Urakawa, N. (1982b). Effects of Li-substitution on high K-indued contractions of

various smooth muscle tissues in the guinea-pig. Jpn. J. Pharmacol. 32: 563-572.

Kishimoto, T., Ozaki, H. & Urakawa, N. (1980). A quantitative relationship between cellular Na

accumulation and relaxation produced by ouabain in the depolarized smooth muscle of

guinea-pig taenia coli. Naunyn-Schmiedeberg's Arch. 312: 199-207.Kishimoto, T., Ozaki, H., Karaki, H., Urakawa, N. & Ishida, Y. (1982). The inhibitory effect of

monensin on high K-induced contraction in guinea-pig taenia coli. Europ. J. Pharmacol. 84:

25-32.

Krishnamurty, V.S.R., Adams, H.R., Smitherman, T.C., Templeton, G.H. & Willerson, J.T. (1977).

Influence of mannitol on contractile responses of isolated perfused arteries. Am. J. Physiol.

232: H59-H66.

Kroeger, E.A., Marshall, J.M. & Bianchi, C.P. (1975). Effects of isoproterenol and D600 on calcium

movements in rat myometrium. J. Pharmacol. Exp. Ther. 193: 309-316.

Kuriyama, H. (1963). The influence of potassium, sodium and chloride on the membrand potential of

the smooth muscle of taenia coli. J. Physiol. 166 : 15-28.

Kuriyama, H., Ohshima, K. & Sakamoto, Y. (1971). The membrane properties of the smooth muscle

of the guinea-pig portal vein in isotonic and hypertonic solutions. J. Physiol. 217 : 179-199.

Lowe, D.A., Matthews, E.K. & Richardson, B.P. (1981). The calcium antagonistic effects of cyprohe-

ptadine on contraction, membrane electrical events and calcium flux in the guinea-pig taenia coli. Br. J. Pharmacol. 74: 651-663.

MacKnight, A.D.C. & Leaf, A. (1977). Regulation of cell volume. Pharmacol. Rev. 57: 510-573.

Meisheri, K.D., Hwang, O. & van Breemen, C. (1981). Evidence for two separate Ca2+ pathways in

smooth muscle plasmalemma. J. Membrane Biol. 59: 19-25.

Mekata, F. (1976). Rectification in the smooth muscle membrane of rabbit aorta. J. Physiol. 258:

269-278.

Murakami, K., Karaki, H., Nakagawa, H. & Urakawa, N. (1983). The inhibitory effect of X537A on

vascular and intestinal smoth muscle contraction. Naunyn-Schmiedeberg's Arch. 325: 80-84.


Nakagawa, H., Karaki, H. & Urakawa, N. (1983). Effects of antimycin A (AA) on smooth muscle

contractions. Abstracts of the Nineth International Congress of Pharmacology. 843P.

Nakajo, S., Shimizu, K., Kometani, A., Kato, K., Kamizaki, J., Isogai, A. & Urakawa, N. (1982).

Inhibitory effect of bassianolide, a cyclodepsipeptide, on drug-induced contractions of iso-

lated smooth muscle preparations. Jpn. J. Pharmacol. 32: 55-64.

Nakajo, S., Shimizu, K., Kometani, A., Suzuki, A., Ozaki, H. & Urakawa, N. (1983). On the inhibitory

mechanism of bassianolide, a cyclodepsipeptide, in acetylcholine-induced contraction in

guinea-pig taenia coli. Jpn. J. Pharmacol. 33: 573-582.Nakayama, K. & Kato, H. (1980). Effects of excess Ca and hypertonic solution on tension develop-

ment in electrically stimulated coronary and cerebral arteries. Differentiation between two

forms of contractile activation. Jpn. J. Pharmacol. 30 (suppL): 171P.

Namm, D.H. & Zucker, J.H.L. (1973). Biochemical alterations caused by hypoxia in the isolated

rabbit aorta. Circulation Res. 32 : 464-470.

Nasu, T. & Urakawa, N. (1973). Effect of cholinergic drugs on calcium movement in guinea pig

taenia coli. Jpn. J. Pharmacol. 23: 553-561.

Nasu, T., Karaki, H., Ikeda, M. & Urakawa, N. (1971). Effects of histamine on calcium movement

in guinea pig taenia coli. Jpn. J. Pharmacol. 21: 597-603.

Nasu, T., Yui, K., Nakagawa, H. & Ishida, Y. (1982). Role of glycolysis in the tension development

under anoxia in guinea pig taenia coli. Jpn. J. Pharmacol. 32: 65-71.

Niedergerke, R. (1956). The potassium chloride contracture of the heart and its modification by

calcium. J. Physiol. 134: 584-599.

Ohashi, H., Takewaki, T. & Okada, T. (1974). Calcium and the contractile effect of carbachol in the

depolarized guinea-pig taenia caecum. Jpn. J. Pharmacol. 24: 601-611.

Ohashi, H., Takewaki, T., Shibata, N. & Okada, T. (1975). Effects of calcium antagonists on

contractile response of guinea-pig taenia caecum to carbachol in a calcium-deficient,

potassium-rich solution. Jpn. J. Pharmacol. 25: 214-217.Ozaki, H. & Urakawa, N. (1979). Na-Ca exchange and tension development in guinea-pig aorta.

Naunyn-Schmiedeberg's Arch. 309: 171-178.

Ozaki, H. & Urakawa, N. (1980). Effects of vanadate on mechanical responses andNa-K pump in

vascular smooth muscle. Europ. J. Pharmacol. 68: 339-347.

Ozaki, H. & Urakawa, N. (1981a). Involvement of Na-Ca exchange mechanism in contraction

induced by low-Na solution in isolated guinea-pig aorta. Pfluger's Arch. 390: 107-112.

Ozaki, H. & Urakawa, N. (1981b). Effects of K-free solution on tension development and Na content

in vascular smooth muscle isolated from guinea-pig, rat and rabbit. Pfliiger's Arch. 389:

189-193.

Ozaki, H., Karaki, H. & Urakawa, N. (1978). Possible role of Na-Ca exchange mechanism in the

contractions induced in guinea-pig aorta by potassium free solution and ouabain. Naunyn-

Schmiedeberg's Arch. 304: 203-209.

Paul, P.J. (1980). Chemical energetics of vascular smooth muscle. In: Handbook of physiology,

section 2, The cardiovascular system, vol. 2, Vascular smooth muscle. Edited by Bohr, D.F.,

Somlyo, A.P. & Sparks, H.V. pp.201-235, Williams & Wilkins Co., Baltimore.

Pfaffman, M., Urakawa, N. & Holland, W.C. (1965). Role of metabolism in K-induced tension

changes in guinea pig taenia coli. Am. J. Physiol. 208: 1203-1205.

Riemer, J., Dorfler, F., Mayer, C.J. & Ulbrecht, G. (1974). Calcium-antagonistic effects on the

spontaneous activity of guinea-pig taenia coli. Pflfiger's Arch. 351: 241-258.

Saito, Y., Sakai, Y., Ikeda, M. & Urakawa, N. (1968). Oxygen consumption during potassium

induced contracture in guinea pig taenia coli. Jpn. J. Pharmacol. 18, 321-331.

Schultz, S.G. & Curran, P.F. (1970). Coupled transport of sodium and organic solutes. Physiol. Rev.

50: 637-718.


Schumann, H.J., Gorlitz, B.D. & Wagner, J. (1975). Influence of papaverine, D600 and nifedipine on the effects of noradrenaline and calcium on the isolated aorta and mesenteric artery of the

rabbit. Naunyn-Schmiedeberg's Arch. 289: 409-418.

Shimizu, K., Nakajo, S. & Urakawa, N. (1983). A comparative study on the contractions induced by high K, Na deficient solution in the gall bladder, trachea or urinary bladder in guinea pig .

Jpn. J. Pharmacol. 34: 231-239.Shimo, Y. & Holland, W.C. (1966). Effects of potassium on membrane potential, spike discharge, and

tension in taenia coli. Am. J. Physiol. 211: 1299-1304.

Somlyo, A.V. & Somlyo, A.P. (1970). Vascular smooth muscle. II. Pharmacology of normal and

hypertensive vessels. Physiol. Rev 22: 249-353.

Somlyo, A.P., Somlyo, A.V. & Smiesko, V. (1972). Cyclic AMP and vascular smooth muscle. In:

Advances in cyclic nucleotide research. Edited by Paoletti, R. & Robinson, G.A. pp.175-194,

Raven Press, N.Y.

Sunano, S. & Shimodan, M. (1981). Factors affecting high-potassium-induced contracture of guinea

pig was deferens. Jpn. J. Physiol. 31: 1-13.Suzuki, T., Karaki, H. & Urakawa, N. (1980). Mechanism of inhibition of contraction by high K, Na

deficient solution in smooth muscle of guinea pig taenia coli. Arch. Int. Pharmacodyn. 248:

43-49.

Suzuki, T., Karaki, H. & Urakawa, N. (1981). Inhibition of contraction by swelling of vascular

smooth muscle in high KCl, low Na solution. Arch. Int. Pharmacody. 250: 195-203.

Thorens, S. & Haeusler, G. (1979). Effects of some vasodilators on calcium translocation in intact

and fractionated vascular smooth muscle. Europ. J. Pharmacol. 54: 79-91.Triggle, D.J. (1981). Calcium antagonists . Basic chemical and pharmacological aspects. In: New

perspectives on calcium antagonists. Edited by Weiss, G.B. pp. 1-18, Williams & Wilkins Co. Baltimore.

Tsuda, S., Urakawa, N. & Saito, Y. (1977). The inhibitory effect of papaverine on respiration

dependent contracture of guinea pig taenia coli in high K medium. I. The relationship

between contracture and respiration. Jpn. J. Pharmacol. 27: 833-843.

Turlapaty, P.D.M.V., Altura, B.T. & Altura, B.M. (1978). Influences of Tris on contractile responses

of isolated rat aorta and portal vein. Am. J. Physiol. 235: H208-H213.

Turlapaty, P.D.M.V., Altura, B.T. & Altura, B.M. (1979a). Effects of Tris on vascular smooth muscle

(Replay). Am. J. Physiol. 236: H410-H411.Turlapaty, P.D.M.V., Altura, B.T. & Altura, B.M. (1979b). Interactions of tris buffer and ethanol on

agonist-induced responses of vascular smooth muscle and on calcium-45 uptake . J. Phar-macol. Exp. Ther. 211: 59-67.

Ueda, F., Kishimoto, T., Ozaki, H. & Urakawa, N. (1982). Dual effects of vanadate on high K-

induced contraction in guinea-pig taenia coli. Jpn. J. Pharmacol. 32: 149-157.Ueda, F., Kishimoto, T., Karaki, H. & Urakawa, N. (1983). K-induced contractions in rabbit and

monkey tracheal smooth muscle. Jpn. J. Smooth Muscle Res. 19: 541-549.Urakawa, N. & Holland, W.C. (1964). Ca' uptake and tissue calcium in K-induced phasic and tonic

contraction in taenia coli. Am. J. Physiol. 207: 873-876.

Urakawa, N., Karaki, H. & Ikeda, M. (1967). Effects of anion substitution on potassium-induced

phasic and tonic contraction in taenia coli. Jpn. J. Pharmacol. 17: 258-266.Urakawa, N., Karaki, H. & Ikeda, M. (1968). 45Ca uptake and tissue Ca of guinea pig taenia coli in

isotonic high K/Na deficient medium. Jpn. J. Pharmacol. 18: 294-298 . Van Breemen, C. (1969). Blockade of membrane calcium flux by lanthanum in relation to vascular

smooth muscle contractility. Arch. Int. Physiol. Biochim. 77: 710-716.Van Breemen, C. (1977). Calcium requirement for activation of intact aortic smooth muscle . J.

Physiol. 272: 317-329.


Van Breemen, C. & McNaughton, E. (1970). The separation of cell membrane calcium transport

from extracellular calcium exchange in vascular smooth muscle. Biochem. Biophys. Res.

Commun. 39: 567-574.

Van Breemen, C., Farinas, B.R., Gerba, P. & McNaughton, E.D. (1972). Excitation-contraction

coupling in rabbit aorta studied by the lanthanum method for measuring cellular calcium

influx. Circulation Res. 30: 44-54.

Van Breemen, C., Aaronson, P., & Loutzenhiser, R. (1979). Na+, Ca2+ interactions in mammarian

smooth muscle. Pharmacol. Rev. 30: 167-208.

Van Breemen, C., Aaronson, P. & Loutzenheiser, R. (1980). The influence of Na+ on Ca2+ flux in the

guinea pig taenia coli. In: Vascular neuroeffector mechanism. Edited by Bevan, J.A., Godfraind, T., Maxwell, P.A. & Vanhautte, P.M. pp.227-237, Raven Press, N.Y.

Van Breemen, C., Hwang, O. & Meisheri, K.D. (1981). The mechanism of inhibitory action of

diltiazem on vascular smooth muscle contractility. J. Pharmacol. Exp. Ther. 218: 459-463.

Waugh, W.W. (1962). Role of calcium in contractile excitation of vascular smooth muscle by

norepinephrine and potassium. Circulation Res. 11: 927-935.

Weiss, G.B. (1975). Stimulation with high potassium. In: Methods in pharmacology, Vol. 3, Smooth

muscle. Edited by Daniel, E.E & Paton, D.M. pp. 339-345, Plenum Press, N.Y.

Weiss, G.B. (1977). Calcium and contractility in vascular smooth muscle. In: Advances in general

and cellular pharmacology, vol. 2. Edited by Narahashi, T. & Bianchi, C.P. pp. 71-154,

Plenum Press, N.Y.

Weiss, G.B. (1981). Sites of action of calcium antagonists in vascular smooth muscle. In: New

perspectives on calcium antagonists. Edited by Weiss, G.B. pp. 83-94, Williams & Wilkins, Baltimore.

Potassium—induced Contraction in Smooth Muscle

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