Effect of benzodiazepine ligands on Ca2+ channel currents in Xenopus oocytes injected with rat heart RNA

J Basic Clin Physiol Pharmacol. 1992 Jan-Mar;3(1):81-97. doi: 10.1515/jbcpp.1992.3.1.81.

Abstract

Voltage-dependent Ca2+ channel (VDCC) currents have been measured in Xenopus oocytes injected with heart RNA purified from 7 day old rats, using voltage clamp technique. The currents were evoked by depolarizing voltage steps, using Ba2+ as charge carrier. Electrophysiological analysis of the current revealed two components: a slow, L-type, dihydropyridine (DHP)-sensitive current and a transient, DHP-insensitive, current. The benzodiazepine (BZ) ligands diazepam and Ro5-4864 decreased the current with micromolar affinity, with potency order of Ro5-4864 greater than diazepam greater than clonazepam. The central antagonist Ro15-1788 did not interfere with the effect of these drugs, thus excluding the possible involvement of the "central type" receptor. The slow current that was increased about 3 fold in the presence of 0.5 microM Bay K 8644, was less potentiated when previously treated with Ro5-4864 or diazepam. Current-voltage relation of the peak inward current and the steady state activation curve showed a small shift towards negative potentials in the presence of 50 microM diazepam. It is concluded that the benzodiazepine ligands block DHP-sensitive voltage dependent Ca2+ channels with a very marginal effect on the transient, DHP-insensitive current. Also it is emphasized that Xenopus oocytes can serve as a useful model system to study the pharmacology of these important drugs on cardiac Ca2+ channels.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Barium / metabolism
  • Benzodiazepines / pharmacology*
  • Benzodiazepinones / pharmacology
  • Calcium Channels / drug effects*
  • Calcium Channels / physiology
  • Clonazepam / pharmacology
  • Diazepam / pharmacology
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Female
  • Myocardium / chemistry*
  • Oocytes
  • RNA / genetics*
  • Rats
  • Xenopus laevis

Substances

  • Benzodiazepinones
  • Calcium Channels
  • Benzodiazepines
  • Barium
  • 4'-chlorodiazepam
  • Clonazepam
  • RNA
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Diazepam