2Na

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Ca Ca Na H 2Na H Cyt Cyt ATP Sarcolemma I Ca Ca Ca 3Na SR RyR 3Na Ca T-Tubule Na Na Na Na Ca NCX NCX ATP 2K ATP PLB AP (E m ) [Ca] i Contraction 3Na 2K ATP by D.M. Bers

description

2K. 2K. Na. Na. Na. ATP. 3Na. Ca. 2Na. Ca. H. Na. H. Cyt. 3Na. ATP. ATP. NCX. Sarcolemma. Na. Ca. Ca. PLB. RyR. ATP. I Ca. SR. Ca. Ca. [Ca] i. NCX. AP (E m ). T-Tubule. 3Na. Contraction. by D.M. Bers. 2K. Na. Na. Na. ATP. 3Na. Ca. 2Na. Ca. H. Na. H. - PowerPoint PPT Presentation

Transcript of 2Na

Page 1: 2Na

Ca

CaNa

H

2Na

H

CytCyt

ATPATP

Sarcolemma

ICa

Ca

Ca

3Na

SR

RyR

3Na

Ca

T-T

ub

ule

NaNaNa

Na

Ca

NCXNCX

NCXNCXATPATP

2K

ATPATP

PLBPLB

AP(Em)

[Ca]i

Contraction

3Na

2K

ATPATP

by D.M. Bers

Page 2: 2Na

Ca

CaNa

H

2Na

H

CytCyt

Ca

RyR

T-T

ub

ule

3Na

Ca

Na

Sarcolemma

NCXNCX AP(Em)

[Ca]i

Contraction

ATPATP

ATPATP NCXNCX

Na 3Na Na

3Na

2K

ATPATP

PLBPLB

ICa

SR

by D.M. Bers

Ca

Na

Ca

Page 3: 2Na

Ca

RyR

3Na

Ca

T-T

ub

ule

NCXNCX

Na Na2K

ATPATPNCXNCXATPATPSarcolemma

3Na Na

ATPATPPLBPLB

AP(Em)

[Ca]i

Contraction

3Na

2K

ATPATP

Ca

CaNa

H

2Na

H

CytCyt

ICa

SR

by D.M. Bers

Ca

Na

Ca

Page 4: 2Na

Sarcolemma

ICa

CaCa

Ca

Ca

3Na

Myofil

Ca

SRR

yR

Ca

Ventricular Myocyte

3Na

Ca

T-T

ub

ule

Na-CaX

Na-CaXATP

PLB ATP

K

Na

Cl

Ca

CaNa

H2Na

H

Cyt

Mito

3Na

2K

ATP

PLM

by D.M. Bers

Page 5: 2Na

Crossbridge CycleChemical steps &

Physical steps correlate

http://www.sci.sdsu.edu/movies/actin_myosin.html

Page 6: 2Na

Crossbridge CycleChemical steps &

Physical steps correlate

http://www.sci.sdsu.edu/movies/actin_myosin.html

Page 7: 2Na

Smooth Muscle EC-Coupling

Pharmaco-mechanicalCoupling

or inhibited K channel

Pharmaco-electrical coupling

Ca entry & Depol

Phasic IP3- & SR-dependent

Tonic Ca2+ influx-dependent (store operated Ca entry)

and [Ca]i elevation via store-operated Ca channels

-60 -40 -20 0 200.0

0.5

1.0f d

ActivationAvailability

Em (mV)

Ca

chan

nel

Co

nd

uct

ance

ICa "Window"Current

ICa can occur during tonic depol. at -50 to -15 mV

ICa driven APsor

Electro-mechanical coupling

DAG-PKC

Page 8: 2Na

Smooth Muscle EC-Coupling

Pharmaco-mechanicalCoupling

Ca entry & Depol

Pharmaco-electrical coupling

Electro-mechanical coupling

cGMP stimulates MLC dephosporylation relaxation

Many agents work via cGMP & cAMP

RyR

IK(Ca)

cAMP stimulates SR Ca uptake, spontaneous local Ca release (Ca sparks) & Ca-activated K current hyperpolarization & relaxation