Hamburg Little is known about the effects of mechanical unloading on cellular Ca2+ handling of the left ventricle. To address this issue, hearts of male Lewis rats were unloaded by heterotopic cardiac transplantation. After two weeks of unloading the density of the L- type Ca2+ current (ICa,L ) was significantly increased by ~50% in endo- and epicardial myocytes. The kinetic properties of ICa,L were not affected, indicating unchanged ion channel composition. Furthermore, no T-type Ca2+ currents were detected. Unloading significantly increased action potential (AP) duration in endo- and epicardial myocytes and reduced the transmural gradient in AP duration. The total AP induced Ca2+ influx (QCa ) was estimated using AP voltage-clamp technique and was significantly increased by ~80% in endo- and by ~370% in epicardial myocytes of unloaded hearts.

We have previously reported that LV unloading leads to a decrease in repolarizing K+ currents. The increase in ICa,L observed in the present study may further contribute to the AP prolongation. Moreover, the increase in QCa may underlie the improved contractility in left ventricular unloading reported by others. These results suggest that left ventricular unloading increases QCa and hence [Ca2+ ]i via two mechanisms: by a decrease in repolarizing K+ currents and a concurrent increase in L-type Ca2+ current density.