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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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 Kmfor 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.

Original languageEnglish
Pages (from-to)125-136
Number of pages12
JournalJournal of Membrane Biology
Volume132
Issue number2
DOIs
StatePublished - Mar 1993
Externally publishedYes

Keywords

  • Ca
  • K channel
  • fused MDCK cells
  • minoxidil-sulfate
  • protein kinase C

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