R- and L-type Ca2+ channels are insensitive to eliprodil in rat cultured cerebellar granule neurons

Eur J Pharmacol. 1997 Apr 4;323(2-3):277-81. doi: 10.1016/s0014-2999(97)00141-6.

Abstract

We have investigated, by using the whole-cell patch-clamp technique, the Ca2+ channel antagonist properties of eliprodil in cultured cerebellar granule cells which are known to express L-, N-, P- as well as Q- and R-type Ca2+ channels. Eliprodil maximally antagonized 50% of the voltage-dependent Ba2+ current with an IC50 of 4 microM. omega-Conotoxin-GVIA (3.2 microM) and omega-agatoxin-IVA (0.5 microM) blocked 28 and 43% of the current, respectively. When eliprodil (30 microM) was added to omega-conotoxin-GVIA or omega-agatoxin-IVA the magnitude of the maximal inhibition was identical to that obtained with eliprodil alone confirming a full blockade by eliprodil of N-, P- and Q-type Ca2+ channels. The L-type channel antagonist nimodipine (10 microM) blocked 24% of the current; this blockade was fully additive to that of eliprodil, indicating that the nimodipine-sensitive component of the current is eliprodil-insensitive. In the presence of eliprodil and nimodipine a residual Cd2+ sensitive current (25%), identified as the R-type current, remained unblocked. We conclude that in cerebellar granule neurons R- and L-type Ca2+ channels are insensitive to eliprodil. The nimodipine-sensitive channels present in cerebellar granule neurons may represent a neuronal subtype of L channels distinct from that (eliprodil-sensitive/nimodipine-sensitive) present in cortical or hippocampal neurons.

MeSH terms

  • Animals
  • Barium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / drug effects*
  • Cerebellum / metabolism
  • Drug Interactions
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nimodipine / pharmacology
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Piperidines / pharmacology*
  • Rats
  • Spider Venoms / pharmacology
  • omega-Agatoxin IVA
  • omega-Conotoxin GVIA

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Peptides
  • Piperidines
  • Spider Venoms
  • omega-Agatoxin IVA
  • Barium
  • Nimodipine
  • omega-Conotoxin GVIA
  • eliprodil