Inhibition of the interaction of G protein G(o) with calcium channels by the calcium channel beta-subunit in rat neurones

J Physiol. 1995 Jun 1;485 ( Pt 2)(Pt 2):365-72. doi: 10.1113/jphysiol.1995.sp020735.


1. The beta-subunit has marked effects on the biophysical and pharmacological properties of voltage-dependent calcium channels. In the present study we examined the ability of the GABAB agonist (-) -baclofen to inhibit calcium channel currents in cultured rat dorsal root ganglion neurones following depletion of beta-subunit immunoreactivity, 108-116 h after microinjection of a beta-subunit antisense oligonucleotide. 2.We observed that, although the calcium channel current was markedly reduced in amplitude following beta-subunit depletion, the residual current (comprising both N- and L-type calcium channel currents) showed an enhanced response to application of (-) -baclofen. Therefore, it is possible that there is normally competition between activated G protein G(o) and the calcium channel beta-subunit for binding to the calcium channel alpha 1-subunit; and this competition shifts in favour of the binding of activated G(o) following depletion of the beta-subunit, resulting in increased inhibition. 3. This hypothesis is supported by evidence that an antibody against the calcium channel beta-subunit completely abolishes stimulation of the GTPase activity of G(o) by the dihydropyridine agonist S-(-) -Bay K 8644 in brain membranes. This stimulation of GTPase is thought to result from an interaction of G(o) alpha-subunit (G alpha o) with its calcium channel effector which may operate as a GTPase-activating protein. 4. These data suggest that the calcium channel beta-subunit when complexed with the beta 1-subunit normally inhibits its association with activated G(o). It may function as a GTPase-activating protein to reduce the ability of activated G(o) to associate with the calcium channel, and thus limit the efficacy of agonists such as (-) -baclofen.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Baclofen / pharmacology
  • Base Sequence
  • Calcium Channel Agonists / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Cells, Cultured
  • Electrophysiology
  • GTP Phosphohydrolases / metabolism
  • GTP-Binding Proteins / metabolism*
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Immunohistochemistry
  • Molecular Sequence Data
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oligonucleotides, Antisense / pharmacology
  • Rats


  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Calcium Channels
  • Oligonucleotides, Antisense
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Baclofen