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Heart Molecules to Cells

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BIOL 1840U
Peter Cheung

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Outline of Lecture 37 (05-21 A; Marban and O’Rourke) Heart Molecules to Cells I. Differences between cardiac and skeletal muscle II. Three factors affect contractile force 1) Intracellular calcium: higher [Ca]inives higher force 2) Contractile protein response to intracellular calcium: e.g. regulation by phosphorylation 3) Loading: higher preload gives higher afterload force III. Steps in E-C Coupling 1) Depolarization opens L-type Ca channels in t-tubules, and allows Ca entry directly over the SR membrane 2) Ca-induced Ca release: Ca induces ryanodine receptors in SR membrane to allow additional Ca out of SR (positive feedback system, regulation poorly understood) 3) Ca binds to troponin C and allows crossbridge cycling and force generation 4) Ca removed from cytosol by SR Ca ATPase (reputake into SR) and Ca/Na exchange (and, minorly, sarcolemmal Ca ATPase) IV. Contractile proteins - Force vs. [Ca]ins a steep sigmoid - cAMP-dependent phosphorylation of troponin regulates its Ca responsiveness V. Autonomic regulation Symp stimulation  β-adrengic cascade  ↑cAMP  cAMP-dependent protein kinase  phosphorylate… 1) L-type Ca channels: increase Ca influx, ionotropic 2) Phospholamban: accelerate Ca uptake into SR
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