Potentiation of the cardiac L-type Ca(2+) channel (alpha(1C)) by dihydropyridine agonist and strong depolarization occur via distinct mechanisms.
A defining property of L-type Ca(2+) 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 (alpha(1C)) are linked. We found that the mutant L-type channel GFP-alpha(1C)(TQ-->YM), 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 alpha(1C) are distinct. Since neither GFP-CACC nor GFP-CCAA was potentiated significantly by depolarization, no single repeat of alpha(1C) appears to be responsible for depolarization-induced potentiation. Surprisingly, GFP-CACC displayed a low estimated open probability similar to that of the alpha(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.
Wilkens
C M
CM
Department of Anatomy and Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Grabner
M
M
Beam
K G
KG
D000200:Action Potentials; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; C038806:1,4-dihydropyridine