Y1 s1 membrane potentials
Transcript of Y1 s1 membrane potentials
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Excitable Tissues, Resting Membrane Potential & Action
PotentialProf. Vajira Weerasinghe
Professor of PhysiologyDepartment of Physiology
Faculty of Medicinewww.slideshare.net/vajira54
MED1102 Foundation to Human Physiology
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Excitable Tissues• Tissues which are capable of generation and
transmission of electrochemical impulses along the membrane
Nerve
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Excitable tissuesexcitable Non-excitable
Red cellGIT
neuron
muscle
•RBC•Intestinal cells•Fibroblasts•Adipocytes
•Nerve •Muscle
•Skeletal•Cardiac•Smooth
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Membrane potential
• A potential difference exists across all cell membranes
• This is called – Resting Membrane Potential (RMP)
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Membrane potential
– Inside is negative with respect to the outside– This is measured using microelectrodes and
oscilloscope – This is about -70 to -90 mV
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Excitable tissues
• Excitable tissues have more negative RMP ( - 70 mV to - 90 mV)
excitable Non-excitable
Red cellGIT
neuron
muscle
• Non-excitable tissues have less negative RMP
-53 mV epithelial cells-8.4 mV RBC-20 to -30 mV fibroblasts-58 mV adipocytes
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Resting Membrane Potential• This depends on following factors
– Ionic distribution across the membrane– Membrane permeability – Other factors
• Na+/K+ pump
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Ionic distribution
• Major ions– Extracellular ions
• Sodium, Chloride– Intracellular ions
• Potassium, Proteinate
K+ Pr-
Na+ Cl-
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Ionic distribution
Ion Intracellular ExtracellularNa+ 10 142K+ 140 4Cl- 4 103
Ca2+ 0 2.4
HCO3- 10 28
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Gibbs Donnan Equilibrium• When two solutions
containing ions are separated by membrane that is permeable to some of the ions and not to others an electrochemical equilibrium is established
• Electrical and chemical energies on either side of the membrane are equal and opposite to each other
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Flow of Potassium
• Potassium concentration intracellular is more• Membrane is freely permeable to K+
• There is an efflux of K+
K+ K+K+
K+K+ K+K+
K+
K+K+
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Flow of Potassium
• Entry of positive ions in to the extracellular fluid creates positivity outside and negativity inside
K+ K+K+
K+K+ K+K+
K+
K+K+
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Flow of Potassium
• Outside positivity resists efflux of K+
• (since K+ is a positive ion)• At a certain voltage an equilibrium is reached
and K+ efflux stops
K+ K+K+
K+K+ K+K+
K+
K+K+
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Nernst potential (Equilibrium potential)
• The potential level across the membrane that will exactly prevent net diffusion of an ion
• Nernst equation determines this potential
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Nernst potential (Equilibrium potential)
• The potential level across the membrane that will exactly prevent net diffusion of an ion
Ion Intracellular Extracellular Nernst potential
Na+ 10 142 +60K+ 140 4 -90Cl- 4 103 -89
Ca2+ 0 2.4 +129
HCO3- 10 28 -23
(mmol/l)
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Goldman Equation• When the membrane is permeable to several ions the
equilibrium potential that develops depends on– Polarity of each ion– Membrane permeability– Ionic conc
• This is calculated using Goldman Equation (or GHK Equation)
• In the resting state– K+ permeability is 20 times more than that of Na+
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Ionic channels
• Leaky channels (leak channels)– Allow free flow of ions– K+ channels (large number) – Na+ channels (fewer in number)– Therefore membrane is more permeable to K+
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Na/K pump
• Active transport system for Na+-K+ exchange using energy
• It is an electrogenic pump since 3 Na+ efflux coupled with 2 K+ influx
• Net effect of causing negative charge inside the membrane
3 Na+
2 K+
ATP ADP
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Factors contributing to RMP• One of the main factors is K+ efflux (Nernst Potential:
-90mV)• Contribution of Na+ influx is little (Nernst Potential:
+60mV)• Na+/K+ pump causes more negativity inside the
membrane• Negatively charged protein ions remaining inside the
membrane contributes to the negativity
• Net result: -70 to -90 mV inside
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Electrochemical gradient• At this electrochemical equilibrium, there is an exact
balance between two opposing forces:
• Chemical driving force = ratio of concentrations on 2 sides of membrane (concentration gradient)
• The concentration gradient that causes K+ to move from inside to outside taking along positive charge and
• Electrical driving force = potential difference across membrane
• opposing electrical gradient that increasingly tends to stop K+ from moving across the membrane
• Equilibrium: when chemical driving force is balanced by electrical driving force
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Action potential
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Action Potential (A.P.)
• When an impulse is generated– Inside becomes positive – Causes depolarisation– Nerve impulses are transmitted as AP
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Dep
olar
isat
ion R
epolarisation
-70
+30
RMP
Hyperpolarisation
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Inside of the membrane is• Negative
– During RMP
• Positive– When an AP is generated
-70
+30
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• Initially membrane is slowly depolarised• Until the threshold level is reached
– (This may be caused by the stimulus)
-70
+30
Threshold level
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• Then a sudden change in polarisation causes sharp upstroke (depolarisation) which goes beyond the zero level up to +35 mV
-70
+30
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• Then a sudden decrease in polarisation causes initial sharp down stroke (repolarisation)
-70
+30
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• When reaching the Resting level rate slows down
• Can go beyond the resting level– hyperpolarisation
-70
+30
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• Spike potential– Sharp upstroke and
downstroke
• Time duration of AP– 1 msec
-70
+30
1 msec
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All or none law• Until the threshold level the potential is graded• Once the threshold level is reached
– AP is set off and no one can stop it !– Like a gun
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All or none law• The principle that the strength by which a nerve
or muscle fiber responds to a stimulus is not dependent on the strength of the stimulus
• If the stimulus is any strength above threshold, the nerve or muscle fiber will give a complete response or otherwise no response at all
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Physiological basis of AP• When the threshold level is reached
– Voltage-gated Na+ channels open up– Since Na conc outside is more than the inside– Na influx will occur– Positive ion coming inside increases the positivity of the membrane
potential and causes depolarisation
– When it reaches +30, Na+ channels closes– Then Voltage-gated K+ channels open up– K+ efflux occurs– Positive ion leaving the inside causes more negativity inside the membrane– Repolarisation occurs
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Physiological basis of AP• Since Na+ has come in and K+ has gone out• Membrane has become negative• But ionic distribution has become unequal
• Na+/K+ pump restores Na+ and K+ conc slowly– By pumping 3 Na+ ions outward and 2+ K ions
inward
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VOLTAGE-GATED ION CHANNELS
• Na+ channel– This has two gates
• Activation and inactivation gates
outside
inside
Activation gate
Inactivation gate
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• At rest: the activation gate is closed• At threshold level: activation gate opens
– Na+ influx will occur– Na+ permeability increases to 500 fold
• when reaching +30, inactivation gate closes– Na influx stops
• Inactivation gate will not reopen until resting membrane potential is reached• Na+ channel opens fast
outsideinside
outsideinside
-70 Threshold level +30Na+ Na+
outsideinside
Na+m gate
h gate
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VOLTAGE-GATED K+ Channel
• K+ channel– This has only one gate
outside
inside
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– At rest: K+ channel is closed– At +30
• K+ channel open up slowly• This slow activation causes K efflux
– After reaching the resting still slow K+ channels may remain open: causing further hyperpolarisation
outsideinside
outsideinside
-70 At +30
K+ K+
n gate
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Summary
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Refractory Period• Absolute refractory
period– During this period nerve
membrane cannot be excited again
– Because of the closure of inactivation gate
-70
+30
outside
inside
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Refractory Period• Relative refractory
period– During this period nerve
membrane can be excited by supra threshold stimuli
– At the end of repolarisation phase inactivation gate opens and activation gate closes
– This can be opened by greater stimuli strength
-70
+30
outside
inside
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Propagation of AP
• When one area is depolarised• A potential difference exists between that site
and the adjacent membrane• A local current flow is initiated• Local circuit is completed by extra cellular fluid
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Propagation of AP
• This local current flow will cause opening of voltage-gated Na channel in the adjacent membrane
• Na influx will occur • Membrane is deloparised
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Propagation of AP
• Then the previous area become repolarised• This process continue to work• Resulting in propagation of AP
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Propagation of AP
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Propagation of AP
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Propagation of AP
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Propagation of AP
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Propagation of AP
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Propagation of AP
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Propagation of AP
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Propagation of AP
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AP propagation along myelinated nerves
• Na channels are conc around nodes
• Therefore depolarisation mainly occurs at nodes
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AP propagation along myelinated nerves
• Local current will flow one node to another• Thus propagation of A.P. is faster. Conduction
through myelinated fibres also faster.• Known as Saltatory Conduction
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• Re-establishment of Na & K conc after A.P.– Na-K Pump is responsible for this. – Energy is consumed
3 Na+
2 K+
ATP ADP
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Membrane stabilisers• Membrane stabilisers (these decrease excitability)
• Increased serum Ca++– Hypocalcaemia causes membrane instability and spontaneous activation of nerve
membrane– Reduced Ca level facilitates Na entry– Spontaneous activation
• Decreased serum K+• Local anaesthetics• Acidosis• Hypoxia
• Membrane destabilisers (these increase excitability)• Decreased serum Ca++• Increased serum K+• Alkalosis
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Muscle action potentials • Skeletal muscle• Smooth muscle• Cardiac muscle
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Skeletal muscle • Similar to nerve action potential
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Cardiac muscle action potentialPhases• 0: depolarisation• 1: short
repolarisation• 2: plateau phase• 3: repolarisation • 4: resting
Duration is about 250 msec
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Cardiac muscle action potentialPhases• 0: depolarisation
(Na+ influx through fast Na+ channels)
• 1: short repolarisation (K+ efflux through K+
channels, Cl- influx as well)• 2: plateau phase
(Ca++ influx through slow Ca++ channels)
• 3: repolarisation (K+ efflux through K+
channels)• 4: resting
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Smooth muscle • Resting membrane potential may be about -55mV
• Action potential is similar to nerve AP
• But AP is not necessary for its contraction
• Smooth muscle contraction can occur by hormones
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Depolarisation • Activation of nerve membrane• Membrane potential becomes positive• Due to influx of Na+ or Ca++
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Hyperpolarisation • Inhibition of nerve membrane• Membrane potential becomes more negative• Due to efflux of K+ or influx of Cl-