Adaptation in membrane Ca2+ channels as a basis for alcohol-related pathology

This paper is a review, based largely though not exclusively on work from the authors' research group, of the role of Ca2+ channels in the actions of ethanol. The position is taken that an important consequence of the presence of ethanol in the region of excitable cells is a reduction in voltage-activation of membrane ion channels with a resulting decrease in cellular excitability. We suggest that excitable cells adapt to this effect by increasing the number of Ca2+ channels on the cell membrane. The channels are of a subtype which are inhibited by the dihydropyridine Ca2+ “antagonist” drugs. Although the mechanism of Ca2+ channel up-regulation is an effective short-term measure as adaptation against the acute effects of ethanol, we consider it may have detrimental longer term consequences including physical dependence and alcohol-related pathology including the death of excitable cells.