Role of the GTP-binding protein G(o) in the suppressant effect of ethanol on voltage-activated calcium channels of murine sensory neurons.
Whole-cell and single-channel recording techniques were used to investigate the acute, in vitro effects of ethanol on the function of voltage-activated Ca2+ channels in cultured neurons derived from dorsal root ganglia (DRG) of embryonic mice. Although 5.4 mM ethanol produced a sustained increase of the amplitude of the whole-cell Ca2+ current (ICa), 43.2 mM ethanol had a time-dependent biphasic effect. That is, within 0.5 min of exposure to 43.2 mM ethanol, the maximal amplitude of ICa initially increased before declining to a new steady-state value. As anticipated, the facilitatory and inhibitory effects of ethanol on ICa were associated with an increase and decrease, respectively, in the probability of single-channel open events. Pretreatment of DRG with 200 ng/ml of pertussis toxin abolished the inhibitory, but not the facilitatory, effect of 43.2 mM ethanol on ICa. Pretreatment with pertussis toxin also prevented the reduction of the probability of single-channel opening caused by 43.2 mM ethanol. Similarly, dialysis of neurons with polyclonal antibodies against the alpha-subunit of G(o) but not Gs, abolished the inhibitory effect of 43.2 mM ethanol on ICa. These data demonstrate concentration- and time-dependent biphasic effects of ethanol on the activity of Ca2+ channels. The inhibitory effect of ethanol requires activation of the alpha-subunit of G(o), which then decreases the probability of Ca2+ channel opening.
Huang
G J
GJ
Department of Pharmacology and Toxicology, New Jersey Medical School (UMDNJ), Newark 07103-2714.
McArdle
J J
JJ
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D037342:Pertussis Toxin; D011247:Pregnancy; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D010566:Virulence Factors, Bordetella; D000431:Ethanol; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins