Two high-voltage-activated, dihydropyridine-sensitive Ca2+ channel currents with distinct electrophysiological and pharmacological properties in cultured rat aortic myocytes.
In smooth muscle cells, essentially two distinct types of voltage-gated Ca2+ channels have been shown, on the basis of their distinct electrophysiological and pharmacological properties, to coexist. Here we report that, in addition to a dihydropyridine (DHP)-sensitive, low-voltage-activated Ba2+ current (IBa,LVA), two types of high-voltage-activated Ba2+ currents with distinct waveforms were recorded in whole-cell clamped aortic myocytes; these were referred to as IBa,HVA1 and IBa,HVA2. They were investigated in cells where no IBa,LVA was detectable. IBa,HVA1 had a slow, monoexponential decay. In contrast, the decay of IBa,HVA2 was much faster and biexponential. In addition, IBa,HVA2 had more negative ranges of activation and steady-state inactivation than IBa,HVA1 and was more sensitive to the DHP antagonist nicardipine (concentrations for half maximum inhibition 0.2 microM and 2 microM, respectively). When using the physiological ion Ca2+ as the charge carrier, the decay of HVA1 currents was not altered, whereas both time constants of HVA2 current decay were accelerated five-fold. Moreover, permeability ratios (ICa/IBa) were also significantly different (0.2 and 0.6 for HVA1 and HVA2 respectively). IBa,HVA1 and IBa,HVA2 are consistent either with the existence and activation of two functionally distinct subtypes of the so-called "DHP-sensitive L-type" Ca2+ channel or with different gating behaviours of a single type of channel. Potentially, they may serve distinct biological functions and constitute distinct targets for neurotransmitters and drugs.
Neveu
D
D
Centre de Recherches de Biochimie Macromoléculaire, C.N.R.S. UPR 9008, I.N.S.E.R.M. U 249, Montpellier, France.
Nargeot
J
J
Richard
S
S
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004095:Dihydropyridines / Q000494:pharmacology*; D004553:Electric Conductivity; D004594:Electrophysiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D004095:Dihydropyridines; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D009529:Nicardipine