Dual modulation of renal ATP-sensitive K+ channel by protein kinases A and C

W. Wang, G. Giebisch

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

A small-conductance K+ channel in the apical membrane of rat cortical collecting duct (CCD) cells controls K+ secretion in the kidney. Previously, we observed that the activity of the channel is stimulated by cAMP-dependent protein kinase A (PKA)-induced channel phosphorylation. We now have applied the patch-clamp technique to study the effects of protein kinase C (PKC) on the secretory K+ channel of rat CCD. In cell-attached patches, application of phorbol 12-myristate 13-acetate progressively reduced the open probability and current amplitude of the K+ channel. In inside-out patches, administration of PKC reversibly decreased the channel open probability (P(o)) without changing the channel conductance. The PKC-induced inhibition of channel activity was Ca2+ dependent: P(o) decreased 42%, 23%, and 11% in the presence of 1000 nM, 100 nM, and 10 nM free Ca2+, respectively. We also demonstrate that PKC antagonizes the stimulatory effect of PKA on the apical K+ secretory channel of rat CCD. These results suggest regulation of K+-channel activity by two separate sites of phosphorylation with distinct and opposite effects on channel activity.

Original languageEnglish
Pages (from-to)9722-9725
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number21
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • cortical collecting duct
  • ion channels
  • rat kidney

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