Actions of ethanol on voltage-sensitive sodium channels: effects on neurotoxin-stimulated sodium uptake in synaptosomes.
Exposure of rat brain synaptosomes to ethanol in vitro reduced the neurotoxin-stimulated uptake of 22Na+. This effect of ethanol was concentration-dependent, occurred with concentrations of ethanol achieved in vivo and was fully reversible. The inhibitory effect of ethanol on neurotoxin-stimulated sodium uptake was due to a decrease in the maximal effect of the neurotoxins. Ethanol reduced the rate of batrachotoxin-stimulated sodium uptake when measured at 3, 5 and 7 but not 10 or 20 sec after the addition of 22Na+. In a series of aliphatic alcohols, there was a good correlation between potency for inhibition of batrachotoxin-stimulated 22Na+ uptake and the membrane/buffer partition coefficient, suggesting that a hydrophobic site in the membrane was involved in the action of the alcohols. Ethanol did not affect the scorpion venom-induced enhancement of batrachotoxin-stimulated sodium uptake. The inhibitory potency of tetrodotoxin was also unaffected by ethanol. These results demonstrate that ethanol has an inhibitory effect on neurotoxin-stimulated sodium influx occurring in voltage-sensitive sodium channels of brain tissue.
Mullin
M J
MJ
Hunt
W A
WA
D000818:Animals; D001496:Batrachotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004563:Electrochemistry; D000431:Ethanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D012995:Solubility; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D001496:Batrachotoxins; D007473:Ion Channels; D009498:Neurotoxins; D000431:Ethanol; D013779:Tetrodotoxin; D012964:Sodium