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

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Abstract
Objectives: The aim of the present study was to assess and compare the dynamics of L-type Ca2+ current (ICa,L) during physiologic action potential (AP) in canine ventricular cardiomyocytes of epicardial (EPI) and endocardial (ENDO) origin. Methods:ICa,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 ICa,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 ICa,L profiles, and increased the net charge entry carried by ICa,L during the AP from 0.187±0.059 to 0.262±0.056 pC/pF (n = 5, PICa,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:ICa,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 ICa,L could be well explained with differences in AP configuration.

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