title: Chronic ethanol exposure induces an N-type calcium channel splice variant with altered channel kinetics.
abstract: 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.
authors.affiliation: Department of Neurology, University of California at San Francisco, The Ernest Gallo Clinic and Research Center, Emeryville, CA 94608, USA. pnewton@egcrc.net
authors.forename: Philip M
authors.initials: PM
authors.lastname: Newton
authors.forename: Keith
authors.initials: K
authors.lastname: Tully
authors.forename: Thomas
authors.initials: T
authors.lastname: McMahon
authors.forename: Jackie
authors.initials: J
authors.lastname: Connolly
authors.forename: Jahan
authors.initials: J
authors.lastname: Dadgar
authors.forename: Steven N
authors.initials: SN
authors.lastname: Treistman
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
mesh_terms: 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
chemical_list: D020864:Calcium Channels, N-Type; D017931:DNA Primers; D012333:RNA, Messenger; D000431:Ethanol