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Pflugers Arch
2008 Nov 01;4572:417-30. doi: 10.1007/s00424-008-0534-1.
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Introduction into Ca(v)2.1 of the homologous mutation of Ca(v)1.2 causing the Timothy syndrome questions the role of V421 in the phenotypic definition of P-type Ca(2+) channel.
Cens T, Leyris JP, Charnet P.
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The Timothy syndrome is a multisystem disorder associated with the mutation of a Gly residue (G402 or G406) in the Ca(v)1.2 Ca(2+) channel. G406 is localized at the end of the IS6 segment and just before the intracellular I-II loop, which is important for the regulation of channel inactivation and the binding of the Ca(v)beta subunit. This Gly residue is conserved in all Ca(v)1 and Ca(v)2 channels, and the G to R exchange produces a strong decrease of inactivation not only in Ca(v)1.2 but also in Ca(v)2.3. Here, we show that the mutation into Arg or Glu of the homologous Gly residue in Ca(v)2.1 (G363) produces also a slowing of inactivation. However, the G-to-A exchange that decreases the inactivation rate in Ca(v)1.2 and Ca(v)2.3 increases inactivation in Ca(v)2.1. Each mutation affects specifically the gating properties of Ca(v)2.1 that remain nevertheless modulated by the co-expressed beta subunit as with wild-type channel. The strong decrease of inactivation produced by the G363R or G363E mutations was reminiscent to that previously described for a specific splice variant of Ca(v)2.1 that contains a single Val residue inserted in the I-II loop (V421). We unexpectedly found that the V421 insertion does not affect the inactivation rate of Ca(v)2.1 and that the effects previously attributed to this insertion, including those on G-protein regulation, can be reproduced by the G363E mutation. Altogether, our results highlight the role of G363 in gating properties, inactivation kinetics, and G-protein regulation of Ca(v)2.1 and the lack of effect of V421 insertion on inactivation.
Agler,
G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels.
2005, Pubmed
Agler,
G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels.
2005,
Pubmed Agler,
Custom distinctions in the interaction of G-protein beta subunits with N-type (CaV2.2) versus P/Q-type (CaV2.1) calcium channels.
2003,
Pubmed Alseikhan,
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2002,
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The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels.
2008,
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Amino acids in segment IVS6 and beta-subunit interaction support distinct conformational changes during Ca(v)2.1 inactivation.
2001,
Pubmed
,
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2007,
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Splicing of alpha 1A subunit gene generates phenotypic variants of P- and Q-type calcium channels.
1999,
Pubmed
,
Xenbase Budde,
Calcium-dependent inactivation of neuronal calcium channels.
2002,
Pubmed Cantí,
Interaction between G proteins and accessory subunits in the regulation of 1B calcium channels in Xenopus oocytes.
2000,
Pubmed
,
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1999,
Pubmed Cens,
Voltage- and calcium-dependent inactivation in high voltage-gated Ca(2+) channels.
2006,
Pubmed
,
Xenbase Chaudhuri,
Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca2+ current.
2005,
Pubmed Currie,
Comparison of N- and P/Q-type voltage-gated calcium channel current inhibition.
1997,
Pubmed De Waard,
How do G proteins directly control neuronal Ca2+ channel function?
2005,
Pubmed De Waard,
Subunit regulation of the neuronal alpha 1A Ca2+ channel expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase Dolphin,
Beta subunits of voltage-gated calcium channels.
2003,
Pubmed Erxleben,
Cyclosporin and Timothy syndrome increase mode 2 gating of CaV1.2 calcium channels through aberrant phosphorylation of S6 helices.
2006,
Pubmed Gao,
C-terminal fragments of the alpha 1C (CaV1.2) subunit associate with and regulate L-type calcium channels containing C-terminal-truncated alpha 1C subunits.
2001,
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Helical packing patterns in membrane and soluble proteins.
2004,
Pubmed Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed Kanumilli,
Alternative splicing generates a smaller assortment of CaV2.1 transcripts in cerebellar Purkinje cells than in the cerebellum.
2006,
Pubmed Kiyonaka,
RIM1 confers sustained activity and neurotransmitter vesicle anchoring to presynaptic Ca2+ channels.
2007,
Pubmed Kleiger,
GXXXG and AXXXA: common alpha-helical interaction motifs in proteins, particularly in extremophiles.
2002,
Pubmed Klugbauer,
Calcium channel alpha2delta subunits: differential expression, function, and drug binding.
2003,
Pubmed Kordasiewicz,
C-termini of P/Q-type Ca2+ channel alpha1A subunits translocate to nuclei and promote polyglutamine-mediated toxicity.
2006,
Pubmed Li,
Modulation of inactivation properties of CaV2.2 channels by 14-3-3 proteins.
2006,
Pubmed Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed Lorenzon,
Altered calcium channel currents in Purkinje cells of the neurological mutant mouse leaner.
1998,
Pubmed Mangoni,
Characterisation of alpha 1A Ba2+, Sr2+ and Ca2+ currents recorded with the ancillary beta 1-4 subunits.
1997,
Pubmed
,
Xenbase Mermelstein,
Properties of Q-type calcium channels in neostriatal and cortical neurons are correlated with beta subunit expression.
1999,
Pubmed Patil,
Elementary events underlying voltage-dependent G-protein inhibition of N-type calcium channels.
1996,
Pubmed Pragnell,
Calcium channel beta-subunit binds to a conserved motif in the I-II cytoplasmic linker of the alpha 1-subunit.
1994,
Pubmed Rasmussen,
Crystal structure of the human beta2 adrenergic G-protein-coupled receptor.
2007,
Pubmed Raybaud,
The role of the GX9GX3G motif in the gating of high voltage-activated Ca2+ channels.
2006,
Pubmed
,
Xenbase Restituito,
The [beta]2a subunit is a molecular groom for the Ca2+ channel inactivation gate.
2000,
Pubmed
,
Xenbase Richards,
Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current.
2007,
Pubmed Roche,
Ca2+ channel beta3 subunit enhances voltage-dependent relief of G-protein inhibition induced by muscarinic receptor activation and Gbetagamma.
1998,
Pubmed
,
Xenbase Rousset,
Functional roles of gamma2, gamma3 and gamma4, three new Ca2+ channel subunits, in P/Q-type Ca2+ channel expressed in Xenopus oocytes.
2001,
Pubmed
,
Xenbase Senes,
Folding of helical membrane proteins: the role of polar, GxxxG-like and proline motifs.
2004,
Pubmed Serrano,
Effect of alanine versus glycine in alpha-helices on protein stability.
1992,
Pubmed Shi,
Molecular determinants of voltage-dependent slow inactivation of the Ca2+ channel.
2002,
Pubmed
,
Xenbase Sokolov,
Modulation of slow inactivation in class A Ca2+ channels by beta-subunits.
2000,
Pubmed
,
Xenbase Soong,
Systematic identification of splice variants in human P/Q-type channel alpha1(2.1) subunits: implications for current density and Ca2+-dependent inactivation.
2002,
Pubmed Splawski,
Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.
2004,
Pubmed
,
Xenbase Splawski,
Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.
2005,
Pubmed
,
Xenbase 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 Stotz,
Fast inactivation of voltage-dependent calcium channels. A hinged-lid mechanism?
2000,
Pubmed Stotz,
Identification of inactivation determinants in the domain IIS6 region of high voltage-activated calcium channels.
2001,
Pubmed Tsunemi,
Novel Cav2.1 splice variants isolated from Purkinje cells do not generate P-type Ca2+ current.
2002,
Pubmed Weiss,
Importance of voltage-dependent inactivation in N-type calcium channel regulation by G-proteins.
2007,
Pubmed Xie,
Localization of the activation gate of a voltage-gated Ca2+ channel.
2005,
Pubmed
,
Xenbase Xu,
The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse.
2005,
Pubmed Zhang,
Molecular determinants of voltage-dependent inactivation in calcium channels.
1994,
Pubmed
,
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