G-proteins are involved in riluzole inhibition of high voltage-activated calcium channels in rat dorsal root ganglion neurons

Brain Res. 1997 Jul 11;762(1-2):235-9. doi: 10.1016/s0006-8993(97)00491-5.

Abstract

Effects of riluzole on high voltage-activated (HVA) calcium channels of rat dorsal root ganglion neurons were studied using the whole-cell patch-clamp technique. Riluzole at 30 microM inhibited the HVA currents. The onset and offset of riluzole inhibitory effect were slow usually taking more than 3 min. Riluzole inhibition of the HVA currents was abolished and partially reduced by addition of 500 microM GDP-beta-S and 1 mM N-ethylmaleimide, respectively, to the pipette solution. Pre-treatment with pertussis toxin or application of depolarizing pre-pulses did not affect riluzole's inhibitory effect on the HVA currents. Riluzole inhibition of the HVA currents was also blocked by internal application of 50 microg/ml protein kinase A inhibitory peptide. It was concluded that pertussis toxin-insensitive G-proteins and protein kinase A may be involved in riluzole inhibition of the HVA currents.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium Channels / physiology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Inhibitors / pharmacology
  • Ethylmaleimide / pharmacology
  • GTP-Binding Proteins / metabolism*
  • Ganglia, Spinal / cytology
  • Guanosine Diphosphate / analogs & derivatives
  • Guanosine Diphosphate / pharmacology
  • Ion Channel Gating / drug effects
  • Neurons / chemistry*
  • Neurons / drug effects
  • Neurons / enzymology
  • Neuroprotective Agents / pharmacology*
  • Patch-Clamp Techniques
  • Pertussis Toxin
  • Rats
  • Rats, Sprague-Dawley
  • Riluzole
  • Thiazoles / pharmacology*
  • Thionucleotides / pharmacology
  • Virulence Factors, Bordetella / pharmacology

Substances

  • Calcium Channels
  • Enzyme Inhibitors
  • Neuroprotective Agents
  • Thiazoles
  • Thionucleotides
  • Virulence Factors, Bordetella
  • Guanosine Diphosphate
  • guanosine 5'-O-(2-thiodiphosphate)
  • Riluzole
  • Pertussis Toxin
  • Cyclic AMP-Dependent Protein Kinases
  • GTP-Binding Proteins
  • Ethylmaleimide