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

  • Cell and Molecular Physiology
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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.

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Acknowledgements

We thank A. Tinker for the gift of the KCNQ4 clone and advice, DA. Brown for providing the KCNQ2 and KCNQ3 clones, B. Fakler for the rat prestin clone and M. Stocker for the KCNA1 clone. We thank H. Dorricott and R. Louvel for experimental assistance and J.E. Gale and D.J. Jagger for helpful discussion and critical review of the manuscript. This work was supported by the Wellcome Trust.

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  1. Department of Physiology and Centre for Auditory Research, University College London, Gower Street, London, WC1E 6BT, UK

    J.-M. Chambard & J. F. Ashmore

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Correspondence to J. F. Ashmore.

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Chambard, JM., Ashmore, J.F. Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway. Pflugers Arch - Eur J Physiol 450, 34–44 (2005). https://doi.org/10.1007/s00424-004-1366-2

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