Cardiac Muscle Physiology

Cardiac muscle cells (cardiomyocytes) share the sliding filament mechanism of contraction with skeletal muscle, but have unique features that make the heart a syncytium — many cells acting as one. The key structural difference is the intercalated disc: a specialised junction between adjacent cardiomyocytes that allows both physical and electrical coupling. Gap junctions within intercalated discs permit rapid propagation of action potentials across the entire myocardium.

Excitation-contraction (EC) coupling in cardiac muscle differs importantly from skeletal muscle. When the sarcolemma depolarises, L-type calcium channels (also in T-tubules) open and a small amount of Ca2+ enters the cell (~25% of what is needed). This triggers calcium-induced calcium release (CICR) from the sarcoplasmic reticulum via ryanodine receptors (RYR). The density of RYR near L-type channels and the short nanometre-scale distance between them facilitates this process. The resulting 10-100 fold rise in intracellular Ca2+ allows Ca2+ to bind troponin C, shift tropomyosin, expose actin binding sites, and enable cross-bridge cycling.

Relaxation requires rapid Ca2+ removal by three mechanisms: SERCA (sarcoendoplasmic reticulum Ca2+-ATPase) pumps most Ca2+ back into the SR — its activity is inhibited by phospholamban (PLN) in its dephosphorylated state; the Na+/Ca2+ exchanger extrudes remaining Ca2+ using the Na+ gradient (maintained by Na+/K+-ATPase); and a small amount is pumped out by the plasma membrane Ca2+ ATPase.

Cardiac contractility — performance at a given preload and afterload — is enhanced by sympathetic (β1-adrenergic) stimulation. Noradrenaline binds β1 receptors → G-protein → adenylate cyclase → cAMP → PKA. PKA phosphorylates L-type channels and RYR (more Ca2+ entry → stronger contraction — positive inotropic effect), and phosphorylates PLN (relieves SERCA inhibition → faster Ca2+ removal → faster relaxation — positive lusitropic effect) and troponin-I.

Frank-Starling's Law describes the relationship between ventricular filling (preload/EDV) and output (SV): the more the heart is filled, the greater the SV — up to a point of over-stretching. Increased sympathetic contractility shifts the entire Starling curve upward (higher SV for the same EDV). Positive inotropes (noradrenaline, adrenaline, digoxin) increase contractility; negative inotropes (hypoxia, sepsis, calcium channel blockers, beta-blockers) decrease it.