LIPID SOLUBILITY IS NOT THE SOLE CRITERION FOR THE INHIBITION OF A CA-2+-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. © 1990.