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Role of the GTP‐Binding Protein G o in the Suppressant Effect of Ethanol on Voltage‐Activated Calcium Channels of Murine Sensory Neurons
Author(s) -
Huang GuoJie,
McArdle Joseph J.
Publication year - 1994
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1994.tb00918.x
Subject(s) - gtp' , calcium , ethanol , chemistry , biophysics , sensory system , g protein , voltage dependent calcium channel , microbiology and biotechnology , biochemistry , neuroscience , biology , receptor , enzyme , organic chemistry
Whole‐cell and single‐channel recording techniques were used to investigate the acute, in vitro effects of ethanol on the function of voltage‐activated Ca 2+ 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 Ca 2+ current (I Ca ), 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 I Ca initially increased before declining to a new steady‐state value. As anticipated, the facilitatory and inhibitory effects of ethanol on I Ca 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 I Ca 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 a‐subunit of Go but not G., abolished the inhibitory effect of 43.2 mM ethanol on I Ca These data demonstrate concentration‐ and time‐dependent biphasic effects of ethanol on the activity of Ca 2+ channels. The inhibitory effect of ethanol requires activation of the a‐subunit of Go, which then decreases the probability of Ca 2+ channel opening.