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Mechanism of activation of K++ channels by minoxidil-sulfate in Madin-Darby canine kidney cells

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Summary

We studied the mechanism of K++ channel activation by minoxidil-sulfate (MxSO4) in fused Madin-Darby canine kidney (MDCK) cells. Patch-clamp techniques were used to assess single channel activity, and fluorescent dye techniques to monitor cell calcium. A Ca+2+-dependent inward-rectifying K++ channel with slope conductances of 53±3 (negative potential range) and 20±3 pS (positive potential range) was identified. Channel activity is minimal in cell-attached patches. MxSO4 initiated both transient channel activation and an increase of intracellular Ca+2+ (from 94.2±9.1 to 475±12.6 nmol/liter). The observation that K++ channel activity of excised inside-out patches was detected only at Ca+2+ concentrations in excess of 10 μmol/liter suggests the involvement of additional mechanisms during channel activation by MxSO4.

Transient K++ channel activity was also induced in cell-attached patches by 10 μmol/liter of the protein kinase C activator 1-oleoyl-2-acetyl-glycerol (OAG). OAG (10 μmol/liter in the presence of 1.6 mmol/liter ATP) increased the Ca+2 sensitivity of the K+ channel in inside-out patches significantly by lowering the K mfor Ca+2 from 100 μmol/liter to 100 nmol/liter. The channel activation by OAG was reversed by the protein kinase inhibitor H8. Staurosporine, a PKC inhibitor, blocked the effect of MxSO4 on K+ channel activation. We conclude that MxSO4-induced K+ channel activity is mediated by the synergistic effects of an increase in intracellular Ca+2 and a PKC-mediated enhancement of the K+ channel's sensitivity to Ca+2.

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Authors and Affiliations

  1. Department of Cellular and Molecular Physiology, Yale University School of Medicine, 06510, New Haven, Connecticut

    Albrecht Schwab, John Geibel, Wenhui Wang, Hans Oberleithner & Gerhard Giebisch

  2. Department of Physiology, University of Würzburg, D-8700, Würzburg, Germany

    Albrecht Schwab & Hans Oberleithner

Authors
  1. Albrecht Schwab
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  2. John Geibel
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  3. Wenhui Wang
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  4. Hans Oberleithner
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  5. Gerhard Giebisch
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Additional information

A. Schwab was recipient of a Feodor-Lynen-Fellowship from the Alexander von Humboldt-Stiftung. This work was supported by NIH grant DK 17433. The authors thank Nikon Instruments Partners in Research Program for their support and generous use of equipment during the course of this study. Minoxidil-sulfate was kindly provided by Upjohn, Kalamazoo, MI.

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Schwab, A., Geibel, J., Wang, W. et al. Mechanism of activation of K++ channels by minoxidil-sulfate in Madin-Darby canine kidney cells. J. Membarin Biol. 132, 125–136 (1993). https://doi.org/10.1007/BF00239002

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  • DOI: https://doi.org/10.1007/BF00239002

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