Referenced in: none

Automatically associated channels: Cav1.3 , Slo1

Title: Modulation of Cav1.3 Ca2+ channel gating by Rab3 interacting molecule.

Authors: Mathias Gebhart, Gabriella Juhasz-Vedres, Annalisa Zuccotti, Niels Brandt, Jutta Engel, Alexander Trockenbacher, Gurjot Kaur, Gerald J Obermair, Marlies Knipper, Alexandra Koschak, Jörg Striessnig

Journal, date & volume: Mol. Cell. Neurosci., 2010 Jul , 44, 246-59

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20363327

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.