Inhibition of T-type calcium currents by dihydropyridines in mouse embryonic dorsal root ganglion neurons.
The effects of dihydropyridines (DHPs) normally considered to be specific for L-type calcium channels were studied on the T-type Ca channel current of acutely isolated dorsal root ganglion (DRG) neurons taken from 13-day-old (E13) mouse embryos. Potent but reversible inhibitory effects of the DHP nicardipine were found in the micromolar range. For example, 5 microM nicardipine suppressed 93 +/- 5% of T-type currents. In comparison, other classical DHPs such as nifedipine, PN 200-110 and nitrendipine had only weak effects (less than 20% inhibition) at the same concentration. The inhibition by nicardipine was found slightly to be voltage dependent and the drug induced a leftward shift in the steady-state inactivation. The DHP agonist (-)-Bay K 8644, which dramatically increased the L-type current, weakly decreased T-type Ca currents (17 +/- 8% at 5 microM). In conclusion, neuronal T-type Ca channels may be potential targets for some dihydropyridines. This property is not only a feature of the central nervous system (J. Physiol., 412 (1989) 181-195) and can be extended to peripheral neurons.
Richard
S
S
Centre de Recherches de Biochimie Macromoléculaire, CNRS UPR 8402, INSERM U 249, Montpellier, France.
Diochot
S
S
Nargeot
J
J
Baldy-Moulinier
M
M
Valmier
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004553:Electric Conductivity; D004558:Electric Stimulation; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology
D004095:Dihydropyridines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009529:Nicardipine; D002118:Calcium