title: Structure and functional characterization of neuronal alpha 1E calcium channel subtypes.
abstract: We have cloned overlapping cDNAs encoding alpha 1E Ca2+ channel subunits from mouse and human brain. We observed that these alpha 1E transcripts were widely distributed in the central nervous system. We also demonstrated the existence of two variants of the human alpha 1E subunit. Comparison of the sequence of these alpha 1E subunits to those from other species suggests that at least four alternatively spliced variants of alpha 1E exist. Expression of human alpha 1E in HEK293 cells and Xenopus oocytes produced high voltage-activated Ca2+ currents that inactivated rapidly (tau approximately 20 ms at 0 mV). The size of the currents obtained were enhanced approximately 40-fold by co-expression with human neuronal alpha 2 and beta Ca2+ channel subunits. alpha 1E currents were insensitive to the drugs and toxins previously used to define other classes of voltage-activated Ca2+ channels. Thus, alpha 1E-mediated Ca2+ channels appear to be a pharmacologically distinct class of voltage-activated Ca2+ channels.
authors.affiliation: SIBIA, Inc., La Jolla, California 92037.
authors.forename: M E
authors.initials: ME
authors.lastname: Williams
authors.forename: L M
authors.initials: LM
authors.lastname: Marubio
authors.forename: C R
authors.initials: CR
authors.lastname: Deal
authors.forename: M
authors.initials: M
authors.lastname: Hans
authors.forename: P F
authors.initials: PF
authors.lastname: Brust
authors.forename: L H
authors.initials: LH
authors.lastname: Philipson
authors.forename: R J
authors.initials: RJ
authors.lastname: Miller
authors.forename: E C
authors.initials: EC
authors.lastname: Johnson
authors.forename: M M
authors.initials: MM
authors.lastname: Harpold
authors.forename: S B
authors.initials: SB
authors.lastname: Ellis
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D015640:Ion Channel Gating; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014981:Xenopus
chemical_list: C423009:CACNA1E protein, human; C498916:Cacna1e protein, mouse; D015220:Calcium Channels; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; D011994:Recombinant Proteins