Cardiac muscle and the cardiac cycle

A ventricular or atrial working cell rests near -90 mV because of the inward-rectifier K+ current. When a neighbour depolarises it through gap junctions, voltage-gated Na+ channels open and the membrane shoots to about +20 mV (phase 0). A transient outward K+ current produces the brief notch of phase 1. Phase 2, the plateau, lasts 200 to 300 ms: L-type Ca2+ channels carry inward current that roughly balances the outward delayed-rectifier K+ current, so the membrane stays depolarised. As Ca2+ channels inactivate and K+ currents grow, the cell repolarises (phase 3) and returns to rest (phase 4). Pacemaker cells of the sinoatrial node have no stable rest: the funny current (a Na+ leak through HCN channels opened by hyperpolarisation) and T-type Ca2+ channels drift the membrane from about -60 mV to threshold, the upstroke is carried by L-type Ca2+ channels and is therefore slow, and K+ efflux repolarises. Sympathetic stimulation steepens the drift through cyclic AMP; vagal acetylcholine flattens it and hyperpolarises the cell, slowing the rate.

The action potential travels down the T tubules, which in cardiac muscle lie at the Z line. Ca2+ entering through L-type channels binds ryanodine receptors on the sarcoplasmic reticulum and triggers release of a much larger amount of stored Ca2+, so cytosolic Ca2+ rises about tenfold. Ca2+ binds troponin C, tropomyosin moves off the actin binding sites, and cross-bridge cycling generates force; the force of a beat therefore depends on how much Ca2+ is released, which is what catecholamines, digitalis and extracellular Ca2+ change. Relaxation needs Ca2+ removal by the sarcoplasmic reticulum Ca2+ pump (SERCA, regulated by phospholamban) and by the Na+/Ca2+ exchanger in the sarcolemma. Because the plateau keeps Na+ channels inactivated, the absolute refractory period outlasts the peak of contraction and only a relative refractory period remains during relaxation. A second stimulus cannot summate the twitches, so the heart cannot tetanise, and every contraction is followed by relaxation long enough for filling. A high extracellular K+ depolarises the resting membrane, inactivates Na+ channels and weakens or arrests the heart; high extracellular Ca2+ strengthens contraction and can cause spastic arrest.

Blood moves only down a pressure gradient, and each valve opens or closes when the gradient across it reverses. Late in diastole atrial contraction (after the P wave) adds the last 20 to 30 percent of ventricular filling and produces the a wave in atrial pressure. Ventricular depolarisation (QRS) starts contraction; when ventricular pressure exceeds atrial pressure the mitral and tricuspid valves close (S1) and isovolumic contraction begins, with all four valves shut and volume fixed at the end-diastolic volume of about 120 ml. When left ventricular pressure passes aortic pressure (about 80 mmHg) the aortic valve opens and rapid then reduced ejection follows, pushing pressure to about 120 mmHg and volume down to the end-systolic volume of about 50 ml. As the ventricle repolarises (T wave) and relaxes, its pressure falls below aortic pressure, the aortic valve closes (S2, with the dicrotic notch on the aortic trace) and isovolumic relaxation begins with volume fixed at end-systolic volume. When ventricular pressure falls below atrial pressure the atrioventricular valves open and rapid filling, then diastasis, then atrial systole complete the cycle. At 75 beats per minute the cycle lasts 0.8 s, with systole about 0.3 s; when the rate rises, diastole shortens far more than systole, which limits filling and coronary perfusion.

Plotting left ventricular pressure against volume gives a loop with four sides: filling along the bottom (volume rises at low pressure), isovolumic contraction as a vertical line on the right at end-diastolic volume, ejection along the top (volume falls while pressure stays near arterial pressure) and isovolumic relaxation as a vertical line on the left at end-systolic volume. The width of the loop is the stroke volume (about 70 ml), and the area inside it is the external stroke work. Preload moves the right edge (a larger end-diastolic volume widens the loop), afterload raises the pressure at which the aortic valve opens and moves the left edge rightwards, and contractility steepens the end-systolic pressure–volume line and moves the left edge leftwards. Ejection fraction is stroke volume divided by end-diastolic volume, normally 55 to 70 percent; values below about 40 percent define systolic failure. The first heart sound comes from closure of the atrioventricular valves and the vibration of the ventricular walls at the start of systole, and the second from closure of the semilunar valves at the start of diastole; the aortic component precedes the pulmonary one, and inspiration widens the split by delaying pulmonary closure. A third sound during rapid filling is normal in the young and a sign of a dilated failing ventricle in older adults; a fourth sound is produced by atrial contraction into a stiff ventricle.