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α 1B N‐Type Calcium Channel Isoforms with Distinct Biophysical Properties
Author(s) -
STEA ANTHONY,
DUBEL STEFAN J.,
SNUTCH TERRY P.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb11282.x
Subject(s) - linker , chemistry , glycine , biophysics , kinetics , alanine , calcium channel , amino acid , glutamate receptor , biochemistry , gene isoform , voltage dependent calcium channel , methionine , serine , calcium , stereochemistry , biology , phosphorylation , receptor , gene , physics , organic chemistry , quantum mechanics , computer science , operating system
N‐type calcium channels both generate the initial calcium signal to trigger neurotransmitter release and also interact with synaptic release proteins at many mammalian central nervous system synapses. Two isoforms of the α 1B N‐type channel from rat brain (α 1B‐I and α 1B‐II ) were found to differ in four regions: (1) a glutamate (Glu) to glycine (Gly) substitution in domain I S3; (2) a Gly to Glu substitution in the domain I‐II linker; (3) the insertion or deletion of an alanine (Ala) in the domain I‐II linker; and (4) the presence or absence of serine/phenylalanine/methionine/glycine (SFMG) in the linker between domain III S3‐S4. Comparison of the electrophysiological properties of the α 1B‐I and α 1B‐II N‐type channels shows that they exhibit distinct kinetics as well as altered current‐voltage relations. Utilizing chimeric α 1B‐I and α 1B‐II cDNAs, we show that: (1) the Glu 177 to Gly substitution in domain I S3 increases the rate of activation by ∼15‐fold; (2) the presence or absence of Ala 415 in the domain I‐II linker alters current‐voltage relations by ∼10 mV but does not affect channel kinetics; (3) the substitution of Gly 387 to Glu in the domain I‐II linker also has no effect on kinetics; and (4) the presence or absence of SFMG (1236–1239) in domain III S3‐S4 did not significantly affect channel current‐voltage relations, kinetics, or steady state inactivation. We conclude that molecularly distinct α 1B isoforms are expressed in rat brain and may account for some of the functional diversity of N‐type currents in native cells.