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Alternative splicing in the cytoplasmic II-III loop of the N-type Ca channel alpha 1B subunit: functional differences are beta subunit-specific.
Pan JQ
,
Lipscombe D
.
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Structural diversity of voltage-gated Ca channels underlies much of the functional diversity in Ca signaling in neurons. Alternative splicing is an important mechanism for generating structural variants within a single gene family. In this paper, we show the expression pattern of an alternatively spliced 21 amino acid encoding exon in the II-III cytoplasmic loop region of the N-type Ca channel alpha(1B) subunit and assess its functional impact. Exon-containing alpha(1B) mRNA dominated in sympathetic ganglia and was present in approximately 50% of alpha(1B) mRNA in spinal cord and caudal regions of the brain and in the minority of alpha(1B) mRNA in neocortex, hippocampus, and cerebellum (<20%). The II-III loop exon affected voltage-dependent inactivation of the N-type Ca channel. Steady-state inactivation curves were shifted to more depolarized potentials without affects on either the rate or voltage dependence of channel opening. Differences in voltage-dependent inactivation between alpha(1B) splice variants were most clearly manifested in the presence of Ca channel beta(1b) or beta(4), rather than beta(2a) or beta(3), subunits. Our results suggest that exon-lacking alpha(1B) splice variants that associate with beta(1b) and beta(4) subunits will be susceptible to voltage-dependent inactivation at voltages in the range of neuronal resting membrane potentials (-60 to -80 mV). In contrast, alpha(1B) splice variants that associate with either beta(2a) or beta(3) subunits will be relatively resistant to inactivation at these voltages. The potential to mix and match multiple alpha(1B) splice variants and beta subunits probably represents a mechanism for controlling the plasticity of excitation-secretion coupling at different synapses.
Bean,
Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence.
1989, Pubmed
Bean,
Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence.
1989,
Pubmed
Bezprozvanny,
Functional impact of syntaxin on gating of N-type and Q-type calcium channels.
1995,
Pubmed
,
Xenbase
Bourinet,
Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
1999,
Pubmed
,
Xenbase
Cahill,
Coexpression of cloned alpha(1B), beta(2a), and alpha(2)/delta subunits produces non-inactivating calcium currents similar to those found in bovine chromaffin cells.
2000,
Pubmed
,
Xenbase
Castellano,
Cloning and expression of a neuronal calcium channel beta subunit.
1993,
Pubmed
,
Xenbase
Castellano,
Cloning and expression of a third calcium channel beta subunit.
1993,
Pubmed
,
Xenbase
Catterall,
Interactions of presynaptic Ca2+ channels and snare proteins in neurotransmitter release.
1999,
Pubmed
Charvin,
Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel.
1997,
Pubmed
Coppola,
Molecular cloning of a murine N-type calcium channel alpha 1 subunit. Evidence for isoforms, brain distribution, and chromosomal localization.
1994,
Pubmed
Dubel,
Molecular cloning of the alpha-1 subunit of an omega-conotoxin-sensitive calcium channel.
1992,
Pubmed
Dunlap,
Exocytotic Ca2+ channels in mammalian central neurons.
1995,
Pubmed
Fujita,
Primary structure and functional expression of the omega-conotoxin-sensitive N-type calcium channel from rabbit brain.
1993,
Pubmed
Ghasemzadeh,
The monoamine neurons of the rat brain preferentially express a splice variant of alpha1B subunit of the N-type calcium channel.
1999,
Pubmed
Goldin,
Preparation of RNA for injection into Xenopus oocytes.
1992,
Pubmed
,
Xenbase
Grabowski,
Splicing regulation in neurons: tinkering with cell-specific control.
1998,
Pubmed
Hirning,
Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons.
1988,
Pubmed
Kollmar,
Hair cell-specific splicing of mRNA for the alpha1D subunit of voltage-gated Ca2+ channels in the chicken's cochlea.
1997,
Pubmed
Kongsamut,
The N-type Ca channel in frog sympathetic neurons and its role in alpha-adrenergic modulation of transmitter release.
1989,
Pubmed
Lin,
Identification of functionally distinct isoforms of the N-type Ca2+ channel in rat sympathetic ganglia and brain.
1997,
Pubmed
,
Xenbase
Lin,
Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons.
1999,
Pubmed
,
Xenbase
Ludwig,
Regional expression and cellular localization of the alpha1 and beta subunit of high voltage-activated calcium channels in rat brain.
1997,
Pubmed
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
Perez-Reyes,
Molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes.
1990,
Pubmed
Perez-Reyes,
Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel.
1992,
Pubmed
,
Xenbase
Plummer,
Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons.
1989,
Pubmed
Pragnell,
Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit.
1994,
Pubmed
Pragnell,
Cloning and tissue-specific expression of the brain calcium channel beta-subunit.
1991,
Pubmed
Rettig,
Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25.
1996,
Pubmed
Schorge,
Calcium channel activation stabilizes a neuronal calcium channel mRNA.
1999,
Pubmed
Scott,
Beta subunit heterogeneity in N-type Ca2+ channels.
1996,
Pubmed
Sharp,
Classification of introns: U2-type or U12-type.
1997,
Pubmed
Sheng,
Identification of a syntaxin-binding site on N-type calcium channels.
1994,
Pubmed
Soldatov,
Genomic structure of human L-type Ca2+ channel.
1994,
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
Walker,
A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca2+ channel activation.
1999,
Pubmed
,
Xenbase
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