Functional properties of cardiac L-type calcium channels transiently expressed in HEK293 cells. Roles of alpha 1 and beta subunits.
The cardiac dihydropyridine-sensitive calcium channel was transiently expressed in HEK293 cells by transfecting the rabbit cardiac calcium channel alpha 1 subunit (alpha 1C) alone or in combination with the rabbit calcium channel beta subunit cloned from skeletal muscle. Transfection with alpha 1C alone leads to the expression of inward, voltage-activated, calcium or barium currents that exhibit dihydropyridine sensitivity and voltage- as well as calcium-dependent inactivation. Coexpression of the skeletal muscle beta subunit increases current density and the number of high-affinity dihydropyridine binding sites and also affects the macroscopic kinetics of the current. Recombinant alpha 1C beta channels exhibit a slowing of activation and a faster inactivation rate when either calcium or barium carries the charge. Our data suggest that both an increase in the number of channels as well as modulatory effects on gating underlie the modifications observed upon beta subunit coexpression.
Pérez-García
M T
MT
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kamp
T J
TJ
Marbán
E
E
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D001464:Barium / Q000493:pharmacokinetics; D002118:Calcium / Q000493:pharmacokinetics; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D004594:Electrophysiology; D006801:Humans; D017275:Isradipine / Q000494:pharmacology; D007700:Kinetics; D009124:Muscle Proteins / Q000502:physiology; D009206:Myocardium / Q000737:chemistry; D009568:Nitrendipine / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D002118:Calcium; D017275:Isradipine