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This Article Full Text Full Text (PDF) All Versions of this Article: 579/1/101    most recent jphysiol.2006.122929v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Raybould, N. P. Articles by Housley, G. D. Search for Related Content PubMed PubMed Citation Articles by Raybould, N. P. Articles by Housley, G. D. Related Collections Neuroscience

¹ Department of Physiology, University of Auckland, Private Bag 92019, Auckland, New Zealand

Ca²⁺ signalling is central to cochlear sensory hair cell physiology through its influence on sound transduction, membrane filter properties and neurotransmission. However, the mechanism for establishing Ca²⁺ homeostasis in these cells remains unresolved. Canonical transient receptor potential (TRPC) Ca²⁺ entry channels provide an important pathway for maintaining intracellular Ca²⁺ levels. TRPC3 subunit expression was detected in guinea pig and rat organ of Corti by RT-PCR, and localized to the sensory and neural poles of the inner and outer hair cells (OHCs) by confocal immunofluorescence imaging. A cation entry current with a TRPC-like phenotype was identified in guinea pig and rat OHCs by whole-cell voltage clamp. This slowly activating current was induced by the lowering of cytosolic Ca²⁺ levels ([Ca²⁺]_i) following a period in nominally Ca²⁺-free solution. Activation was dependent upon the [Ca²⁺]_o and was sustained until [Ca²⁺]_i was restored. Ca²⁺ entry was confirmed by confocal fluorescence imaging, and rapidly recruited secondary charybdotoxin- and apamin-sensitive K_Ca currents. Dual activation by the G protein-coupled receptor (GPCR)–phospholipase C–diacylglycerol (DAG) second messenger pathway was confirmed using the analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG). Ion substitution experiments showed that the putative TRPC Ca²⁺ entry current was selective for Na⁺ > K⁺ with a ratio of 1: 0.6. The Ca²⁺ entry current was inhibited by the TRPC channel blocker 2-aminoethyl diphenylborate (2APB) and the tyrosine kinase inhibitor, erbstatin analogue. We conclude that TRPC Ca²⁺ entry channels, most likely incorporating TRPC3 subunits, support cochlear hair cell Ca²⁺ homeostasis and GPCR signalling.

(Received 16 October 2006; accepted after revision 30 November 2006; first published online 7 December 2006)
Corresponding author G. D. Housley: Department of Physiology, University of Auckland, Private Bag 92019, Auckland, New Zealand. Email: g.housley{at}auckland.ac.nz

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