Volume 13 Supplement 1

18th Scientific Symposium of the Austrian Pharmacological Society (APHAR)

Open Access

Regulation of CaV1.3 Ca2+channels in cochlear inner hair cells

  • Alexandra Pinggera1,
  • Niels Brandt2,
  • Gurjot Kaur1,
  • Jutta Engel2 and
  • Jörg Striessnig1Email author
BMC Pharmacology and Toxicology201213(Suppl 1):A49

DOI: 10.1186/2050-6511-13-S1-A49

Published: 17 September 2012

Background

CaV1.3 Ca2+ channels are voltage-gated L-type calcium channels, regulating many different physiological functions including neurotransmitter release in cochlear inner hair cells (IHCs) after sound-evoked stimulation. In IHCs, the CaV1.3 channel shows rapid activation after stimulation with very slow inactivation kinetics, whereas in other tissues (heart and brain) the channel underlies a very strong inactivation. The exact mechanism for the very slow inactivation observed in IHCs is not known so far. Interaction of the auxiliary β subunit with RIM2α, an active zone scaffolding protein, slows down calcium-dependent inactivation (CDI) and voltage-dependent inactivation (VDI); however, it does not fully account for the even slower inactivation kinetics observed in IHCs, as recently published by our lab. RIM binding proteins (RBPs), another group of active zone proteins, are known to interact with RIM and with the CaV1.3 α1 subunit C-terminus. We therefore hypothesized that interaction of the Ca2+ channel with both RIM and RBPs results in a large signaling complex that restrains gating transitions, leading to the slow inactivation kinetics of the CaV1.3 channel in IHCs.

Methods

In order to investigate whether RBP isoforms and RIM proteins are expressed in inner hair cells, we performed nested PCR. Complex formation of RIM and RBPs with the channel after co-expression in a recombinant system was demonstrated by immunofluorescence microscopy.

Results

So far we could detect RIM2α, RBP2 and RBP3 transcripts in immature and mature IHCs with nested PCR. Preliminary immunofluorescence data also show that RIM and RBPs form a complex that binds to channel-derived peptides.

Conclusions

Our results are in agreement with the hypothesis, justifying further experiments. Therefore we will show the co-localization of CaV1.3, RIM and RBP in ribbon synapses of IHCs (immunohistochemistry) and study the functional consequences of such complex formation by patch clamp recordings.

Declarations

Acknowledgements

Supported by the Austrian Science Fund (P20670, W11) and the University of Innsbruck.

Authors’ Affiliations

(1)
Department of Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck
(2)
Department of Biophysics, Saarland University

Copyright

© Pinggera et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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