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Adaptive downregulation of a quinidine-sensitive cation conductance in renal principal cells of TWIK-1 knockout mice

  • Renal Function, Body Fluids
  • Published:
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Abstract

TWIK-1, a member of the two-pore domain K+ channel family, is expressed in brain, kidney, and lung. The aim of this study was to examine the effect of loss of TWIK-1 on the renal cortical collecting duct. Ducts were isolated from wild-type and TWIK-1 knockout mice by enzyme digestion and whole-cell clamp obtained via the basolateral membrane. Current- and voltage-clamp approaches were used to examine K+ conductances. No difference was observed between intercalated cells from wild-type or knockout ducts. In contrast, knockout principal cells were hyperpolarized compared to wild-type cells and had a reduced membrane conductance. This was a consequence of a fall in a barium-insensitive, quinidine-sensitive conductance (G Quin). G Quin demonstrated outward rectification and had a relatively low K+ to Na+ selectivity ratio. Loss of G Quin would be expected to lead to the hyperpolarization observed in knockout ducts by increasing fractional K+ conductance and Na+ uptake by the cell. Consistent with this hypothesis, knockout ducts had an increased diameter in comparison to wild-type ducts. These data suggest that G Quin contributes to the resting membrane potential in the cortical collecting duct and that a fall in G Quin could be an adaptive response in TWIK-1 knockout ducts.

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Acknowledgements

We gratefully acknowledge the support of the BBSRC and the Physiological Society. I.D. Millar is currently at the Faculty of Life Sciences, University of Manchester.

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Authors and Affiliations

  1. Department of Biomedical Science, University of Sheffield, Sheffield, S10 2TN, UK

    I. D. Millar, H. C. Taylor, G. J. Cooper & L. Robson

  2. Medical Physiology Department, St. George’s University, St. George’s, Grenada, West Indies

    J. D. Kibble

  3. Institut de Pharmacologie du CNRS, 660 Route des Lucioles, Sophia-Antipolis, Valbonne, 06560, France

    J. Barhanin

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  1. I. D. Millar
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Correspondence to L. Robson.

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Millar, I.D., Taylor, H.C., Cooper, G.J. et al. Adaptive downregulation of a quinidine-sensitive cation conductance in renal principal cells of TWIK-1 knockout mice. Pflugers Arch - Eur J Physiol 453, 107–116 (2006). https://doi.org/10.1007/s00424-006-0107-0

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