Endocardial versus epicardial differences in L-type calcium current in canine ventricular myocytes studied by action potential voltage clamp

Objectives: The aim of the present study was to assess and compare the dynamics of L-type Ca2+ current (I-Ca.L) during physiologic action potential (AP) in canine ventricular cardiomyocytes of epicardial (EPI) and endocardial (ENDO) origin. Methods: I-Ca.L was recorded on cells derived from the two regions of the heart using both AP voltage clamp and conventional whole cell voltage clamp techniques. Results: AP voltage clamp experiments revealed that the decay of I-Ca.L is monotonic during endocardial AP, whereas the current is double-peaked (displaying a second rise) during epicardial AP. The amplitude of the first peak was significantly greater in ENDO (-4.6+/-0.8 pA/pF) than in EPI cells (-2.8+/-0.3 pA/pF). Application of epicardial APs as command pulses to endocardial cells yielded double-peaked I-Ca.L profiles, and increased the net charge entry carried by I-Ca.L during the AP from 0.187+/-0.059 to 0.262+/-0.056 pC/pF (n=5, P<0.05). No differences were observed in current densities and inactivation kinetics of I-Ca.L between EPI and ENDO cells when studied under conventional voltage clamp conditions. Nisoldipine shortened action potentials and eliminated the dome of the epicardial AP. Conclusion: I-Ca.L was shown to partially inactivate before and deactivate during phase-1 repolarization and reopening of these channels is responsible for the formation of the dome in canine EPI cells. The transmural differences in the profile of I-Ca.L could be well explained with differences in AP configuration. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.