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.
Newton
Philip M
PM
Department of Neurology, University of California at San Francisco, The Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA. pnewton@egcrc.net
Tully
Keith
K
McMahon
Thomas
T
Connolly
Jackie
J
Dadgar
Jahan
J
Treistman
Steven N
SN
Messing
Robert O
RO
D000818:Animals; D001483:Base Sequence; D020864:Calcium Channels, N-Type / Q000235:genetics*; D017931:DNA Primers; D000431:Ethanol / Q000008:administration & dosage*; D005091:Exons; D016716:PC12 Cells; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014981:Xenopus
D020864:Calcium Channels, N-Type; D017931:DNA Primers; D012333:RNA, Messenger; D000431:Ethanol