Post-rest contraction amplitude in myocytes from failing human ventricle

It has been reported that the balance between the two main Ca2+ removal systems in the cardiac cells, the sarcoplasmic reticulum (SR) and Na+/Ca2+ exchanger, is altered in failing human heart. We have studied post-rest contraction behaviour as a non-invasive probe of the amount of Ca2+ stored in the SR in myocytes from failing and non-failing human ventricle. The first beat following a rest interval, as a percentage of the preceding steady state (B1/SS), was larger and more variable in cells from failing heart, indicating some accumulation of Ca2+ in the SR during rest. This could be mimicked by treatment of myocytes with digoxigenin, a compound which increases intracellular Na+, suggesting that alterations in the Na+ balance of the cell might contribute to the effect. Isoprenaline, which stimulates Ca2+ uptake by the SR while the myocyte is beating, prevented SR Ca2+ accumulation during rest in susceptible myocytes. We hypothesize that loss of SR function in the failing heart is partially compensated for by increased Ca2+ extrusion via the Na+/Ca2+ exchange in the contracting myocyte, leading to increased intracellular Na+ during activity. This Na+ is lost at rest, predisposing the cells to accumulate Ca2+ in the SR. Experiments to test this hypothesis are proposed.