Enhanced sarcolemmal Ca2+ efflux reduces sarcoplasmic reticulum Ca2+ content and systolic Ca2+ in cardiac hypertrophy

Objective: Recent work has identified reductions in the systolic Ca 2+ transient in cardiac disease states. The aim of the present study was to identify the mechanisms responsible for perturbations of intracellular calcium homeostasis in isolated cardiac myocytes and determine if such changes can quantitatively explain the reduced systolic Ca2+ transient. Methods: Left ventricular hypertrophy (LVH) was induced by aortic coarctation in adult ferrets. Changes in intracellular Ca2+ regulation, sarcolemmal Ca2+ fluxes and SR function were measured in single left ventricular cardiac myocytes. Results: Cardiac hypertrophy was associated with a 29% increase in action potential duration (APD90); a 48% reduction in the amplitude of and 19% slowing in the rate of decay of the systolic Ca 2+ transient; a 20% decrease in SR Ca2+ content and a 36% increase in inward Na+-Ca2+ exchange current for a given change in [Ca2+]i (all