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 ) [Ca] i Contraction 3Na 2K ATP by D.M. Bers.

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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 ) [Ca] i Contraction 3Na 2K ATP by D.M. Bers

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

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

Sarcolemma I Ca Ca 3Na Myofil Ca SR RyR Ca Ventricular Myocyte 3Na Ca T-Tubule Na- CaX Na- CaX ATP PLB ATP K Na Cl Ca Na H 2Na H Cyt Mito 3Na 2K ATP PLM by D.M. Bers

Crossbridge Cycle Chemical steps & Physical steps correlate

Crossbridge Cycle Chemical steps & Physical steps correlate

Smooth Muscle EC-Coupling Pharmaco-mechanical Coupling or inhibited K channel Pharmaco-electrical coupling Ca entry & Depol Phasic IP 3 - & SR-dependent Tonic Ca 2+ influx-dependent (store operated Ca entry) and [Ca] i elevation via store-operated Ca channels I Ca can occur during tonic depol. at -50 to -15 mV I Ca driven APs or Electro-mechanical coupling DAG-PKC

Smooth Muscle EC-Coupling Pharmaco-mechanical Coupling Ca entry & Depol Pharmaco-electrical coupling Electro-mechanical coupling cGMP stimulates MLC dephosporylation  relaxation Many agents work via cGMP & cAMP RyR I K(Ca) cAMP stimulates SR Ca uptake, spontaneous local Ca release (Ca sparks) & Ca-activated K current  hyperpolarization & relaxation