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J Neurosci
2002 Mar 01;225:1573-82. doi: 10.1523/JNEUROSCI.22-05-01573.2002.
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Alternative splicing of the beta 4 subunit has alpha1 subunit subtype-specific effects on Ca2+ channel gating.
Helton TD
,
Horne WA
.
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Ca2+ channel beta subunits are important molecular determinants of the kinetics and voltage dependence of Ca2+ channel gating. Through direct interactions with channel-forming alpha1 subunits, beta subunits enhance expression levels, accelerate activation, and have variable effects on inactivation. Four distinct beta subunit genes each encode five homologous sequence domains (D1-5), three of which (D1, D3, and D5) undergo alternative splicing. We have isolated from human spinal cord a novel alternatively spliced beta4 subunit containing a short form of domain D1 (beta4a) that is highly homologous to N termini of Xenopus and rat beta3 subunits. The purpose of this study was to compare the gating properties of various alpha1 subunit complexes containing beta4a with those of complexes containing a beta4 subunit with a longer form of domain D1, beta4b. Expression in Xenopus oocytes revealed that, relative to alpha1A and alpha1B complexes containing beta4b, the voltage dependence of activation and inactivation of complexes containing beta4a were shifted to more depolarized potentials. Moreover, alpha1A and alpha1B complexes containing beta4a inactivated at a faster rate. Interestingly, beta4 subunit alternative splicing did not influence the gating properties of alpha1C and alpha1E subunits. Experiments with beta4 deletion mutants revealed that both the N and C termini of the beta4 subunit play critical roles in setting voltage-dependent gating parameters and that their effects are alpha1 subunit specific. Our data are best explained by a model in which distinct modes of activation and inactivation result from beta-subunit splice variant-specific interactions with an alpha1 subunit gating structure.
Berrou,
Molecular determinants of inactivation within the I-II linker of alpha1E (CaV2.3) calcium channels.
2001, Pubmed,
Xenbase
Berrou,
Molecular determinants of inactivation within the I-II linker of alpha1E (CaV2.3) calcium channels.
2001,
Pubmed
,
Xenbase
Birnbaumer,
Structures and functions of calcium channel beta subunits.
1998,
Pubmed
,
Xenbase
Bourinet,
Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
1999,
Pubmed
,
Xenbase
Cens,
Regulation of Ca-sensitive inactivation of a 1-type Ca2+ channel by specific domains of beta subunits.
1999,
Pubmed
,
Xenbase
De Waard,
Subunit regulation of the neuronal alpha 1A Ca2+ channel expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Ellinor,
Functional expression of a rapidly inactivating neuronal calcium channel.
1993,
Pubmed
,
Xenbase
Fanning,
Protein modules as organizers of membrane structure.
1999,
Pubmed
Hanlon,
Modelling of a voltage-dependent Ca2+ channel beta subunit as a basis for understanding its functional properties.
1999,
Pubmed
Herlitze,
Molecular determinants of inactivation and G protein modulation in the intracellular loop connecting domains I and II of the calcium channel alpha1A subunit.
1997,
Pubmed
Horne,
Molecular diversity of Ca2+ channel alpha 1 subunits from the marine ray Discopyge ommata.
1993,
Pubmed
Jones,
Mechanism of auxiliary subunit modulation of neuronal alpha1E calcium channels.
1998,
Pubmed
Kozak,
An analysis of vertebrate mRNA sequences: intimations of translational control.
1991,
Pubmed
Krovetz,
C-Terminal alternative splicing changes the gating properties of a human spinal cord calcium channel alpha 1A subunit.
2000,
Pubmed
,
Xenbase
Lacerda,
Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel.
1991,
Pubmed
Letts,
The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit.
1998,
Pubmed
Levitan,
It is calmodulin after all! Mediator of the calcium modulation of multiple ion channels.
1999,
Pubmed
Liu,
Identification of three subunits of the high affinity omega-conotoxin MVIIC-sensitive Ca2+ channel.
1996,
Pubmed
Mikami,
Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel.
1989,
Pubmed
,
Xenbase
Mori,
Primary structure and functional expression from complementary DNA of a brain calcium channel.
1991,
Pubmed
,
Xenbase
Olcese,
The amino terminus of a calcium channel beta subunit sets rates of channel inactivation independently of the subunit's effect on activation.
1994,
Pubmed
,
Xenbase
Pan,
Alternative splicing in the cytoplasmic II-III loop of the N-type Ca channel alpha 1B subunit: functional differences are beta subunit-specific.
2000,
Pubmed
,
Xenbase
Pragnell,
Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit.
1994,
Pubmed
Qin,
Identification of a second region of the beta-subunit involved in regulation of calcium channel inactivation.
1996,
Pubmed
,
Xenbase
Scott,
Beta subunit heterogeneity in N-type Ca2+ channels.
1996,
Pubmed
Singer,
The roles of the subunits in the function of the calcium channel.
1991,
Pubmed
,
Xenbase
Stotz,
Fast inactivation of voltage-dependent calcium channels. A hinged-lid mechanism?
2000,
Pubmed
Takahashi,
Different types of calcium channels mediate central synaptic transmission.
1993,
Pubmed
Tareilus,
A Xenopus oocyte beta subunit: evidence for a role in the assembly/expression of voltage-gated calcium channels that is separate from its role as a regulatory subunit.
1997,
Pubmed
,
Xenbase
Turner,
Calcium channels coupled to glutamate release identified by omega-Aga-IVA.
1992,
Pubmed
Walker,
A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca2+ channel alpha 1A subunit.
1998,
Pubmed
Walker,
Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel function.
1998,
Pubmed
Walker,
A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation.
1999,
Pubmed
,
Xenbase
Westenbroek,
Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons.
1990,
Pubmed
Westenbroek,
Localization of Ca2+ channel subtypes on rat spinal motor neurons, interneurons, and nerve terminals.
1998,
Pubmed
Wheeler,
Roles of N-type and Q-type Ca2+ channels in supporting hippocampal synaptic transmission.
1994,
Pubmed
Wittemann,
Synaptic localization and presynaptic function of calcium channel beta 4-subunits in cultured hippocampal neurons.
2000,
Pubmed
Wu,
Calcium channel types with distinct presynaptic localization couple differentially to transmitter release in single calyx-type synapses.
1999,
Pubmed
Zhang,
Molecular determinants of voltage-dependent inactivation in calcium channels.
1994,
Pubmed
,
Xenbase