Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
C-Terminal alternative splicing changes the gating properties of a human spinal cord calcium channel alpha 1A subunit.
Krovetz HS
,
Helton TD
,
Crews AL
,
Horne WA
.
???displayArticle.abstract???
The calcium channel alpha(1A) subunit gene codes for proteins with diverse structure and function. This diversity may be important for fine tuning neurotransmitter release at central and peripheral synapses. The alpha(1A) C terminus, which serves a critical role in processing information from intracellular signaling molecules, is capable of undergoing extensive alternative splicing. The purpose of this study was to determine the extent to which C-terminal alternative splicing affects some of the fundamental biophysical properties of alpha(1A) subunits. Specifically, the biophysical properties of two alternatively spliced alpha(1A) subunits were compared. One variant was identical to an isoform identified previously in human brain, and the other was a novel isoform isolated from human spinal cord. The variants differed by two amino acids (NP) in the extracellular linker between transmembrane segments IVS3 and IVS4 and in two C-terminal regions encoded by exons 37 and 44. Expression in Xenopus oocytes demonstrated that the two variants were similar with respect to current-voltage relationships and the voltage dependence of steady-state activation and inactivation. However, the rates of activation, inactivation, deactivation, and recovery from inactivation were all significantly slower for the spinal cord variant. A chimeric strategy demonstrated that the inclusion of the sequence encoded by exon 44 specifically affects the rate of inactivation. These findings demonstrate that C-terminal structural changes alone can influence the way in which alpha(1A) subunits respond to a depolarizing stimulus and add to the developing picture of the C terminus as a critical domain in the regulation of Ca(2+) channel function.
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
Bourinet,
Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
1999,
Pubmed
,
Xenbase
Catterall,
Structure and function of voltage-gated ion channels.
1995,
Pubmed
Dunlap,
Exocytotic Ca2+ channels in mammalian central neurons.
1995,
Pubmed
Hans,
Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels.
1999,
Pubmed
Jun,
Ablation of P/Q-type Ca(2+) channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the alpha(1A)-subunit.
1999,
Pubmed
Kozak,
An analysis of vertebrate mRNA sequences: intimations of translational control.
1991,
Pubmed
Lee,
Ca2+/calmodulin binds to and modulates P/Q-type calcium channels.
1999,
Pubmed
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
Moreno,
beta subunits influence the biophysical and pharmacological differences between P- and Q-type calcium currents expressed in a mammalian cell line.
1997,
Pubmed
Mori,
Primary structure and functional expression from complementary DNA of a brain calcium channel.
1991,
Pubmed
,
Xenbase
Murphy,
L-type voltage-sensitive calcium channels mediate synaptic activation of immediate early genes.
1991,
Pubmed
Ophoff,
Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4.
1996,
Pubmed
Park,
Dynamic regulation of calcium influx by G-proteins, action potential waveform, and neuronal firing frequency.
1998,
Pubmed
Patil,
Preferential closed-state inactivation of neuronal calcium channels.
1998,
Pubmed
Peterson,
Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium channels.
1999,
Pubmed
Piedras-Renteria,
Increased expression of alpha 1A Ca2+ channel currents arising from expanded trinucleotide repeats in spinocerebellar ataxia type 6.
2001,
Pubmed
Qin,
Direct interaction of gbetagamma with a C-terminal gbetagamma-binding domain of the Ca2+ channel alpha1 subunit is responsible for channel inhibition by G protein-coupled receptors.
1997,
Pubmed
,
Xenbase
Sather,
Distinctive biophysical and pharmacological properties of class A (BI) calcium channel alpha 1 subunits.
1993,
Pubmed
,
Xenbase
Slesinger,
Reopening of Ca2+ channels in mouse cerebellar neurons at resting membrane potentials during recovery from inactivation.
1991,
Pubmed
Soldatov,
Molecular determinants of L-type Ca2+ channel inactivation. Segment exchange analysis of the carboxyl-terminal cytoplasmic motif encoded by exons 40-42 of the human alpha1C subunit gene.
1998,
Pubmed
,
Xenbase
Soldatov,
Molecular structures involved in L-type calcium channel inactivation. Role of the carboxyl-terminal region encoded by exons 40-42 in alpha1C subunit in the kinetics and Ca2+ dependence of inactivation.
1997,
Pubmed
,
Xenbase
Sutton,
P/Q-type calcium channels mediate the activity-dependent feedback of syntaxin-1A.
1999,
Pubmed
Takahashi,
Different types of calcium channels mediate central synaptic transmission.
1993,
Pubmed
Tsien,
Molecular diversity of voltage-dependent Ca2+ channels.
1991,
Pubmed
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
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
Yokoyama,
Biochemical properties and subcellular distribution of the neuronal class E calcium channel alpha 1 subunit.
1995,
Pubmed
Zamponi,
Crosstalk between G proteins and protein kinase C mediated by the calcium channel alpha1 subunit.
1997,
Pubmed
,
Xenbase
Zamponi,
Modulation of voltage-dependent calcium channels by G proteins.
1998,
Pubmed
Zhang,
Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons.
1993,
Pubmed
,
Xenbase
Zhang,
Multiple structural elements in voltage-dependent Ca2+ channels support their inhibition by G proteins.
1996,
Pubmed
,
Xenbase
Zhuchenko,
Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel.
1997,
Pubmed
de Leon,
Essential Ca(2+)-binding motif for Ca(2+)-sensitive inactivation of L-type Ca2+ channels.
1995,
Pubmed