Enhanced Ca2+ Influx through Cardiac L-Type Ca2+ Channels Maintains the Systolic Ca2+ Transient in Cardiac Unloading

Abstract

Purpose The Ca2+ transient couples excitation and contraction in cardiac myocytes. Its magnitude is determined by both, sarcolemmal Ca2+ influx and Ca2+ release from the sarcoplasmic reticulum (SR). Alteration of the Ca2+ transient can cause contractile failure and ventricular arrhythmias. The effect of cardiac atrophy on the cardiac Ca2+ transient and its underlying mechanisms is unknown. Methods and Materials To induce cardiac atrophy we unloaded left ventricles of male Lewis rats for two weeks using heterotopic heart transplantation. The SR Ca2+ content was determined by caffeine induced Ca2+ release. Results The SR Ca2+ content in myocytes isolated from atrophic hearts was ~50% lower than in control myocytes. Similarly, diastolic spark frequency was reduced by ~80% in atrophic cardiac myocytes. Surprisingly, however, systolic Ca2+ transients remained unaffected in spite of the reduced SR Ca2+ content and SR Ca2+ release. Action potential clamping demonstrated a marked prolongation of action potentials in endocardial (~+50%) and epicardial myocytes (~+250%) of atrophic hearts which was associated with a ~2- to 4-fold increased action potential driven sarcolemmal Ca2+ influx. Conclusions These results show that cardiac atrophy causes a large reduction of myocyte SR Ca2+ content. Nevertheless, the systolic Ca2+ transient is maintained by an enhanced sarcolemmal Ca2+ influx which compensates for the reduced Ca2+ release from the unloaded SR.