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

Mol Cell Neurosci. 2010 Jul;44(3):246-59. doi: 10.1016/j.mcn.2010.03.011. Epub 2010 Apr 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Alternative Splicing
  • Animals
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Cells, Cultured
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Hair Cells, Auditory, Inner / cytology
  • Hair Cells, Auditory, Inner / physiology*
  • Humans
  • Ion Channel Gating / physiology*
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Patch-Clamp Techniques
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Two-Hybrid System Techniques
  • rab3 GTP-Binding Proteins / genetics
  • rab3 GTP-Binding Proteins / metabolism*

Substances

  • CACNA1D protein, human
  • Calcium Channels, L-Type
  • Nerve Tissue Proteins
  • Protein Isoforms
  • RIMS1 protein, human
  • Recombinant Fusion Proteins
  • GTP-Binding Proteins
  • rab3 GTP-Binding Proteins