Inhibition of T-type calcium currents by dihydropyridines in mouse embryonic dorsal root ganglion neurons

Neurosci Lett. 1991 Nov 11;132(2):229-34. doi: 10.1016/0304-3940(91)90308-g.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Calcium / physiology*
  • Dihydropyridines / pharmacology*
  • Electric Conductivity
  • Electric Stimulation
  • Electrophysiology
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / physiology*
  • Mice
  • Neurons / physiology*
  • Nicardipine / pharmacology

Substances

  • Dihydropyridines
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Nicardipine
  • Calcium