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Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons.
Lin Z
,
Lin Y
,
Schorge S
,
Pan JQ
,
Beierlein M
,
Lipscombe D
.
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The N-type Ca channel alpha1B subunit is localized to synapses throughout the nervous system and couples excitation to release of neurotransmitters. In a previous study, two functionally distinct variants of the alpha1B subunit were identified, rnalpha1B-b and rnalpha1B-d, that differ at two loci;four amino acids [SerPheMetGly (SFMG)] in IIIS3-S4 and two amino acids [GluThr (ET)] in IVS3-S4. These variants are reciprocally expressed in rat brain and sympathetic ganglia (). We now show that the slower activation kinetics of rnalpha1B-b (DeltaSFMG/+ET) compared with rnalpha1B-d (+SFMG/DeltaET) channels are fully accounted for by the insertion of ET in IVS3-S4 and not by the lack of SFMG in IIIS3-S4. We also show that the inactivation kinetics of these two variants are indistinguishable. Through genomic analysis we identify a six-base cassette exon that encodes the ET site and with ribonuclease protection assays demonstrate that the expression of this mini-exon is essentially restricted to alpha1B RNAs of peripheral neurons. We also show evidence for regulated alternative splicing of a six-base exon encoding NP in the IVS3-S4 linker of the closely related alpha1A gene and establish that residues NP can functionally substitute for ET in domain IVS3-S4 of alpha1B. The selective expression of functionally distinct Ca channel splice variants of alpha1B and alpha1A subunits in different regions of the nervous system adds a new dimension of diversity to voltage-dependent Ca signaling in neurons that may be important for optimizing action potential-dependent transmitter release at different synapses.
Augustine,
Calcium requirements for secretion in bovine chromaffin cells.
1992, Pubmed
Augustine,
Calcium requirements for secretion in bovine chromaffin cells.
1992,
Pubmed
Barry,
Multiple calcium channel transcripts in rat osteosarcoma cells: selective activation of alpha 1D isoform by parathyroid hormone.
1995,
Pubmed
Cestèle,
Voltage sensor-trapping: enhanced activation of sodium channels by beta-scorpion toxin bound to the S3-S4 loop in domain II.
1998,
Pubmed
Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed
Coppola,
Molecular cloning of a murine N-type calcium channel alpha 1 subunit. Evidence for isoforms, brain distribution, and chromosomal localization.
1994,
Pubmed
Cota,
Calcium-channel gating in frog skeletal muscle membrane: effect of temperature.
1983,
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
Ellinor,
Structural determinants of the blockade of N-type calcium channels by a peptide neurotoxin.
1994,
Pubmed
,
Xenbase
Fujita,
Primary structure and functional expression of the omega-conotoxin-sensitive N-type calcium channel from rabbit brain.
1993,
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
Hans,
Structural elements in domain IV that influence biophysical and pharmacological properties of human alpha1A-containing high-voltage-activated calcium channels.
1999,
Pubmed
Heidelberger,
Calcium dependence of the rate of exocytosis in a synaptic terminal.
1994,
Pubmed
Hines,
The NEURON simulation environment.
1997,
Pubmed
Hirning,
Dominant role of N-type Ca2+ channels in evoked release of norepinephrine from sympathetic neurons.
1988,
Pubmed
Hogan,
The structure of the gene encoding the human skeletal muscle alpha 1 subunit of the dihydropyridine-sensitive L-type calcium channel (CACNL1A3).
1996,
Pubmed
Ihara,
Molecular diversity and functional characterization of voltage-dependent calcium channels (CACN4) expressed in pancreatic beta-cells.
1995,
Pubmed
Jones,
Calcium currents in bullfrog sympathetic neurons. II. Inactivation.
1989,
Pubmed
Kammermeier,
High-voltage-activated calcium currents in neurons acutely isolated from the ventrobasal nucleus of the rat thalamus.
1997,
Pubmed
Klöckner,
Properties of three COOH-terminal splice variants of a human cardiac L-type Ca2+-channel alpha1-subunit.
1997,
Pubmed
,
Xenbase
Ligon,
Class A calcium channel variants in pancreatic islets and their role in insulin secretion.
1998,
Pubmed
Lin,
Identification of functionally distinct isoforms of the N-type Ca2+ channel in rat sympathetic ganglia and brain.
1997,
Pubmed
,
Xenbase
Llinás,
Blocking and isolation of a calcium channel from neurons in mammals and cephalopods utilizing a toxin fraction (FTX) from funnel-web spider poison.
1989,
Pubmed
Mainen,
Reliability of spike timing in neocortical neurons.
1995,
Pubmed
Mathur,
Role of the S3-S4 linker in Shaker potassium channel activation.
1997,
Pubmed
,
Xenbase
Miljanich,
Antagonists of neuronal calcium channels: structure, function, and therapeutic implications.
1995,
Pubmed
Mintz,
P-type calcium channels in rat central and peripheral neurons.
1992,
Pubmed
Nakai,
Critical roles of the S3 segment and S3-S4 linker of repeat I in activation of L-type calcium channels.
1994,
Pubmed
Naraghi,
Linearized buffered Ca2+ diffusion in microdomains and its implications for calculation of [Ca2+] at the mouth of a calcium channel.
1997,
Pubmed
Olivera,
Calcium channel diversity and neurotransmitter release: the omega-conotoxins and omega-agatoxins.
1994,
Pubmed
Ophoff,
Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4.
1996,
Pubmed
Perez-Reyes,
Molecular diversity of L-type calcium channels. Evidence for alternative splicing of the transcripts of three non-allelic genes.
1990,
Pubmed
Randall,
Pharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule neurons.
1995,
Pubmed
,
Xenbase
Rogers,
Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit.
1996,
Pubmed
Sather,
Distinctive biophysical and pharmacological properties of class A (BI) calcium channel alpha 1 subunits.
1993,
Pubmed
,
Xenbase
Sheng,
Identification of a syntaxin-binding site on N-type calcium channels.
1994,
Pubmed
Snutch,
Distinct calcium channels are generated by alternative splicing and are differentially expressed in the mammalian CNS.
1991,
Pubmed
,
Xenbase
Soldatov,
Genomic structure of human L-type Ca2+ channel.
1994,
Pubmed
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
Soong,
Structure and functional expression of a member of the low voltage-activated calcium channel family.
1993,
Pubmed
Starr,
Primary structure of a calcium channel that is highly expressed in the rat cerebellum.
1991,
Pubmed
Stea,
Localization and functional properties of a rat brain alpha 1A calcium channel reflect similarities to neuronal Q- and P-type channels.
1994,
Pubmed
,
Xenbase
Swartz,
Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels.
1997,
Pubmed
Takahashi,
Different types of calcium channels mediate central synaptic transmission.
1993,
Pubmed
Tang,
Transfer of voltage independence from a rat olfactory channel to the Drosophila ether-à-go-go K+ channel.
1997,
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
Wang,
Peripheral versus central potencies of N-type voltage-sensitive calcium channel blockers.
1998,
Pubmed
Welling,
Alternatively spliced IS6 segments of the alpha 1C gene determine the tissue-specific dihydropyridine sensitivity of cardiac and vascular smooth muscle L-type Ca2+ channels.
1997,
Pubmed
Wheeler,
Roles of N-type and Q-type Ca2+ channels in supporting hippocampal synaptic transmission.
1994,
Pubmed
Williams,
Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel.
1992,
Pubmed
Yamada,
The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes.
1995,
Pubmed
Yu,
Molecular characterization and nephron distribution of a family of transcripts encoding the pore-forming subunit of Ca2+ channels in the kidney.
1992,
Pubmed
Zamponi,
Beta subunit coexpression and the alpha1 subunit domain I-II linker affect piperidine block of neuronal calcium channels.
1996,
Pubmed
,
Xenbase
Zamponi,
Modulation of voltage-dependent calcium channels by G proteins.
1998,
Pubmed
Zhang,
Molecular determinants of voltage-dependent inactivation in calcium channels.
1994,
Pubmed
,
Xenbase
Zühlke,
Ca2+ channel sensitivity towards the blocker isradipine is affected by alternative splicing of the human alpha1C subunit gene.
1998,
Pubmed
,
Xenbase
