Lipid solubility is not the sole criterion for the inhibition of a Ca2(+)-activated K+ channel by alcohols.
The effect of a homologous series of n-alkanols (C2-C8) on the 86Rb+ influx through charybdotoxin sensitive Ca2(+)-activated K+ channels of rat glioma C6 cells was investigated. The lipid solubility of the n-alkanols was not the sole determinant of the inhibitory potency of these substances for ion flux inhibition. 1-Hexanol for example was about 8-times less potent than one would expect on the basis of its lipid solubility. The introduction of a second OH-group in this molecule (giving 1,6-hexanediol) or a structural shift in the OH-group of 1-hexanol from position 1 to 3 strongly increased the potency of the alcohol. The above data cannot be explained by a pure lipid site of action of the alcohols. Therefore it seems likely that direct effects on protein are involved in the inhibitory action of some of the alcohols.
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Institute of Virology and Immunology, University of Würzburg, F.R.G.
Kress
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Koschel
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D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008055:Lipids / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D012414:Rubidium Radioisotopes; D012995:Solubility; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000438:Alcohols; D008055:Lipids; D015221:Potassium Channels; D012414:Rubidium Radioisotopes; D002118:Calcium