ca na h 2na h cyt atp sarcolemma i ca ca 3na sr ryr 3na ca t-tubule na ca ncx atp 2k atp plb ap (e m...
TRANSCRIPT
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