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

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

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

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

Crossbridge CycleChemical steps &

Physical steps correlate

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

Crossbridge CycleChemical steps &

Physical steps correlate

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

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

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