title: Modulation of Cav1.3 Ca2+ channel gating by Rab3 interacting molecule.
abstract: Neurotransmitter release and spontaneous action potentials during cochlear inner hair cell (IHC) development depend on the activity of Ca(v)1.3 voltage-gated L-type Ca(2+) channels. Their voltage- and Ca(2+)-dependent inactivation kinetics are slower than in other tissues but the underlying molecular mechanisms are not yet understood. We found that Rab3-interacting molecule-2alpha (RIM2alpha) mRNA is expressed in immature cochlear IHCs and the protein co-localizes with Ca(v)1.3 in the same presynaptic compartment of IHCs. Expression of RIM proteins in tsA-201 cells revealed binding to the beta-subunit of the channel complex and RIM-induced slowing of both Ca(2+)- and voltage-dependent inactivation of Ca(v)1.3 channels. By inhibiting inactivation, RIM induced a non-inactivating current component typical for IHC Ca(v)1.3 currents which should allow these channels to carry a substantial window current during prolonged depolarizations. These data suggest that RIM2 contributes to the stabilization of Ca(v)1.3 gating kinetics in immature IHCs.
authors.affiliation: Institute of Pharmacy, Pharmacology and Toxicology, University of Innsbruck, Peter-Mayr-Strasse 1/I, A-6020 Innsbruck, Austria; Center of Molecular Biosciences Innsbruck (CMBI), Innsbruck, Austria.
authors.forename: Mathias
authors.initials: M
authors.lastname: Gebhart
authors.forename: Gabriella
authors.initials: G
authors.lastname: Juhasz-Vedres
authors.forename: Annalisa
authors.initials: A
authors.lastname: Zuccotti
authors.forename: Niels
authors.initials: N
authors.lastname: Brandt
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.forename: Alexander
authors.initials: A
authors.lastname: Trockenbacher
authors.forename: Gurjot
authors.initials: G
authors.lastname: Kaur
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Obermair
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.forename: Alexandra
authors.initials: A
authors.lastname: Koschak
authors.forename: Jörg
authors.initials: J
authors.lastname: Striessnig
mesh_terms: D000200:Action Potentials / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C472073:CACNA1D protein, human; D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C491492:RIMS1 protein, human; D011993:Recombinant Fusion Proteins; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins