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.
Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines.
Xu W
,
Lipscombe D
.
???displayArticle.abstract???
L-type calcium channels regulate a diverse array of cellular functions within excitable cells. Of the four molecularly defined subclasses of L-type Ca channels, two are expressed ubiquitously in the mammalian nervous system (Ca(V)1.2alpha(1) and Ca(V)1.3alpha(1)). Despite diversity at the molecular level, neuronal L-type channels are generally assumed to be functionally and pharmacologically similar, i.e., high-voltage activated and highly sensitive to dihydropyridines. We now show that Ca(V)1.3alpha(1) L-type channels activate at membrane potentials approximately 25 mV more hyperpolarized, compared with Ca(V)1.2alpha(1). This unusually negative activation threshold for Ca(V)1.3alpha(1) channels is independent of the specific auxiliary subunits coexpressed, of alternative splicing in domains I-II, IVS3-IVS4, and the C terminus, and of the expression system. The use of high concentrations of extracellular divalent cations has possibly obscured the unique voltage-dependent properties of Ca(V)1.3alpha(1) in certain previous studies. We also demonstrate that Ca(V)1.3alpha(1) channels are pharmacologically distinct from Ca(V)1.2alpha(1). The IC(50) for nimodipine block of Ca(V)1.3alpha(1) L-type calcium channel currents is 2.7 +/- 0.3 microm, a value 20-fold higher than the concentration required to block Ca(V)1.2alpha(1). The relatively low sensitivity of the Ca(V)1.3alpha(1) subunit to inhibition by dihydropyridine is unaffected by alternative splicing in the IVS3-IVS4 linker. Our results suggest that functional and pharmacological criteria used commonly to distinguish among different Ca currents greatly underestimate the biological importance of L-type channels in cells expressing Ca(v)1.3alpha(1).
Ashcroft,
Stimulus-secretion coupling in pancreatic beta cells.
1994, Pubmed
Ashcroft,
Stimulus-secretion coupling in pancreatic beta cells.
1994,
Pubmed
Avery,
Multiple channel types contribute to the low-voltage-activated calcium current in hippocampal CA3 pyramidal neurons.
1996,
Pubmed
Beam,
Structure, function, and regulation of the skeletal muscle dihydropyridine receptor.
1989,
Pubmed
Bean,
Classes of calcium channels in vertebrate cells.
1989,
Pubmed
Bean,
Nitrendipine block of cardiac calcium channels: high-affinity binding to the inactivated state.
1984,
Pubmed
Bell,
Biophysical properties, pharmacology, and modulation of human, neuronal L-type (alpha(1D), Ca(V)1.3) voltage-dependent calcium currents.
2001,
Pubmed
Berjukow,
Molecular mechanism of calcium channel block by isradipine. Role of a drug-induced inactivated channel conformation.
2000,
Pubmed
,
Xenbase
Boland,
omega-Conotoxin block of N-type calcium channels in frog and rat sympathetic neurons.
1994,
Pubmed
Castellano,
Molecular diversity of Ca2+ channel beta subunits.
1994,
Pubmed
Ellinor,
Functional expression of a rapidly inactivating neuronal calcium channel.
1993,
Pubmed
,
Xenbase
Elmslie,
Reevaluation of Ca2+ channel types and their modulation in bullfrog sympathetic neurons.
1994,
Pubmed
Elmslie,
Identification of the single channels that underlie the N-type and L-type calcium currents in bullfrog sympathetic neurons.
1997,
Pubmed
Ertel,
Nomenclature of voltage-gated calcium channels.
2000,
Pubmed
FRANKENHAEUSER,
The action of calcium on the electrical properties of squid axons.
1957,
Pubmed
Finkbeiner,
Ca2+ channel-regulated neuronal gene expression.
1998,
Pubmed
Fuchs,
Synaptic transmission at vertebrate hair cells.
1996,
Pubmed
Galli,
Apoptosis in cerebellar granule cells is blocked by high KCl, forskolin, and IGF-1 through distinct mechanisms of action: the involvement of intracellular calcium and RNA synthesis.
1995,
Pubmed
Grabner,
Transfer of 1,4-dihydropyridine sensitivity from L-type to class A (BI) calcium channels.
1996,
Pubmed
Hell,
Identification and differential subcellular localization of the neuronal class C and class D L-type calcium channel alpha 1 subunits.
1993,
Pubmed
Hess,
Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists.
,
Pubmed
Hui,
Molecular cloning of multiple subtypes of a novel rat brain isoform of the alpha 1 subunit of the voltage-dependent calcium channel.
1991,
Pubmed
Ihara,
Molecular diversity and functional characterization of voltage-dependent calcium channels (CACN4) expressed in pancreatic beta-cells.
1995,
Pubmed
Kavalali,
Selective potentiation of a novel calcium channel in rat hippocampal neurones.
1994,
Pubmed
Kavalali,
Multiple voltage-dependent mechanisms potentiate calcium channel activity in hippocampal neurons.
1996,
Pubmed
Kollmar,
Predominance of the alpha1D subunit in L-type voltage-gated Ca2+ channels of hair cells in the chicken's cochlea.
1997,
Pubmed
Koschak,
alpha 1D (Cav1.3) subunits can form l-type Ca2+ channels activating at negative voltages.
2001,
Pubmed
Liljelund,
L-Type calcium channels mediate calcium oscillations in early postnatal Purkinje neurons.
2000,
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
Mao,
Neuronal activity-dependent cell survival mediated by transcription factor MEF2.
1999,
Pubmed
Mikami,
Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel.
1989,
Pubmed
,
Xenbase
Mori,
Molecular diversity of voltage-dependent calcium channel.
1993,
Pubmed
Norris,
Reversal of age-related alterations in synaptic plasticity by blockade of L-type Ca2+ channels.
1998,
Pubmed
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,
Molecular characterization of a neuronal low-voltage-activated T-type calcium channel.
1998,
Pubmed
,
Xenbase
Pichler,
Beta subunit heterogeneity in neuronal L-type Ca2+ channels.
1997,
Pubmed
Platano,
Expression of the alpha(2)delta subunit interferes with prepulse facilitation in cardiac L-type calcium channels.
2000,
Pubmed
,
Xenbase
Platzer,
Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels.
2000,
Pubmed
Pragnell,
Cloning and tissue-specific expression of the brain calcium channel beta-subunit.
1991,
Pubmed
Randall,
Pharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule neurons.
1995,
Pubmed
,
Xenbase
Smith,
Permeation and gating properties of the L-type calcium channel in mouse pancreatic beta cells.
1993,
Pubmed
Tottene,
Functional diversity of P-type and R-type calcium channels in rat cerebellar neurons.
1996,
Pubmed
Wakamori,
Auxiliary subunits operate as a molecular switch in determining gating behaviour of the unitary N-type Ca2+ channel current in Xenopus oocytes.
1999,
Pubmed
,
Xenbase
Walker,
Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel function.
1998,
Pubmed
Weisskopf,
L-type voltage-gated calcium channels mediate NMDA-independent associative long-term potentiation at thalamic input synapses to the amygdala.
1999,
Pubmed
Williams,
Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype.
1992,
Pubmed
,
Xenbase
Wilson,
The status of voltage-dependent calcium channels in alpha 1E knock-out mice.
2000,
Pubmed
Yamada,
The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes.
1995,
Pubmed
Zidanic,
Kinetic analysis of barium currents in chick cochlear hair cells.
1995,
Pubmed
