Chronic ethanol exposure induces an N-type calcium channel splice variant with altered channel kinetics.

Chronic ethanol exposure increases the density of N-type calcium channels in brain. We report that ethanol increases levels of mRNA for a splice variant of the N channel specific subunit alpha1 2.2 that lacks exon 31a. Whole cell recordings demonstrated an increase in N-type current with a faster activation rate and a shift in activation to more negative potentials after chronic alcohol exposure, consistent with increased abundance of channels containing this variant. These results identify a novel mechanism whereby chronic ethanol exposure can increase neuronal excitability by altering levels of channel splice variants.