title: Activity-dependent regulation of T-type calcium channels by submembrane calcium ions.
abstract: Voltage-gated Ca2+channels are involved in numerous physiological functions and various mechanisms finely tune their activity, including the Ca2+ion itself. This is well exemplified by the Ca2+-dependent inactivation of L-type Ca2+channels, whose alteration contributes to the dramatic disease Timothy Syndrome. For T-type Ca2+channels, a long-held view is that they are not regulated by intracellular Ca2+. Here we challenge this notion by using dedicated electrophysiological protocols on both native and expressed T-type Ca2+channels. We demonstrate that a rise in submembrane Ca2+induces a large decrease in T-type current amplitude due to a hyperpolarizing shift in the steady-state inactivation. Activation of most representative Ca2+-permeable ionotropic receptors similarly regulate T-type current properties. Altogether, our data clearly establish that Ca2+entry exerts a feedback control on T-type channel activity, by modulating the channel availability, a mechanism that critically links cellular properties of T-type Ca2+channels to their physiological roles.
authors.affiliation: IGF, CNRS, INSERM, University of Montpellier, Montpellier, France.|LabEx 'Ion Channel Science and Therapeutics', Montpellier, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Cazade
authors.affiliation: IGF, CNRS, INSERM, University of Montpellier, Montpellier, France.|LabEx 'Ion Channel Science and Therapeutics', Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bidaud
authors.affiliation: IGF, CNRS, INSERM, University of Montpellier, Montpellier, France.|LabEx 'Ion Channel Science and Therapeutics', Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lory
authors.affiliation: IGF, CNRS, INSERM, University of Montpellier, Montpellier, France.|LabEx 'Ion Channel Science and Therapeutics', Montpellier, France.
authors.forename: Jean
authors.identifier: 0000-0002-6089-5964
authors.initials: J
authors.lastname: Chemin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism*; D002478:Cells, Cultured; D055724:Electrophysiological Phenomena; D025461:Feedback, Physiological; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008810:Mice, Inbred C57BL
chemical_list: D020747:Calcium Channels, T-Type; D002413:Cations, Divalent; D002118:Calcium
keywords: 5-HT; 5-HT3; Cav3.1; Cav3.2; Cav3.3; NMDA; P2X; P2X4; TRP; TRPA1; TRPV1; low-voltage-activated; mouse; neuroscience