Pflügers Archiv

, Volume 450, Issue 1, pp 34–44

Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway

Cell and Molecular Physiology

DOI: 10.1007/s00424-004-1366-2

Cite this article as:
Chambard, JM. & Ashmore, J.F. Pflugers Arch - Eur J Physiol (2005) 450: 34. doi:10.1007/s00424-004-1366-2

Abstract

The potassium channel KCNQ4, expressed in the mammalian cochlea, has been associated tentatively with an outer hair cell (OHC) potassium current, IK,n, a current distinguished by an activation curve shifted to exceptionally negative potentials. Using CHO cells as a mammalian expression system, we have examined the properties of KCNQ4 channels under different phosphorylation conditions. The expressed current showed the typical KCNQ4 voltage-dependence, with a voltage for half-maximal activation (V1/2) of −25 mV, and was blocked almost completely by 200 µM linopirdine. Application of 8-bromo-cAMP or the catalytic sub-unit of PKA shifted V1/2 by approximately −10 and −20 mV, respectively. Co-expression of KCNQ4 and prestin, the OHC motor protein, altered the voltage activation by a further −15 mV. Currents recorded with less than 1 nM Ca2+ in the pipette ran down slowly (12% over 5 min). Buffering the pipette Ca2+ to 100 nM increased the run-down rate sevenfold. Exogenous PKA in the pipette prevented the effect of elevated [Ca2+]i on run-down. Inhibition of the calcium binding proteins calmodulin or calcineurin by W-7 or cyclosporin A, respectively, also prevented the calcium-dependent rapid run-down. We suggest that KCNQ4 phosphorylation via PKA and coupling to a complex that may include prestin can lead to the negative activation and the negative resting potential found in adult OHCs.

Keywords

CochleaHair cellsPotassium channelPhosphorylationPrestinCalcium activated binding proteins

Copyright information

© Springer-Verlag  2005

Authors and Affiliations

  1. 1.Department of Physiology and Centre for Auditory ResearchUniversity College LondonLondonUK