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Original Article

Potentiation of the Cardiac L-Type Ca²⁺ Channel (_1C) by Dihydropyridine Agonist and Strong Depolarization Occur via Distinct Mechanisms

^a Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523
^b Department of Biochemical Pharmacology, University of Innsbruck, A-6020 Innsbruck, Austria
Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.(970) 491-7907

kbeam{at}lamar.colostate.edu

A defining property of L-type Ca²⁺ channels is their potentiation by both 1,4-dihydropyridine agonists and strong depolarization. In contrast, non–L-type channels are potentiated by neither agonist nor depolarization, suggesting that these two processes may by linked. In this study, we have tested whether the mechanisms of agonist- and depolarization-induced potentiation in the cardiac L-type channel (_1C) are linked. We found that the mutant L-type channel GFP-_1C(TQYM), bearing the mutations T1066Y and Q1070M, was able to undergo depolarization-induced potentiation but not potentiation by agonist. Conversely, the chimeric channel GFP-CACC was potentiated by agonist but not by strong depolarization. These data indicate that the mechanisms of agonist- and depolarization-induced potentiation of _1C are distinct. Since neither GFP-CACC nor GFP-CCAA was potentiated significantly by depolarization, no single repeat of _1C appears to be responsible for depolarization-induced potentiation. Surprisingly, GFP-CACC displayed a low estimated open probability similar to that of the _1C, but could not support depolarization-induced potentiation, demonstrating that a relatively low open probability alone is not sufficient for depolarization-induced potentiation to occur. Thus, depolarization-induced potentiation may be a global channel property requiring participation from all four homologous repeats.

Key Words: ion channel modulation • facilitation • muscle

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