Role of large Ca2+-activated K+ channels in regulation of mesangial contraction by nitroprusside and ANP

James D. Stockand, Steven C. Sansom

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The patch-clamp method, in conjunction with measurements of cell contraction, was employed to investigate activation by guanosine 3',5'- cyclic monophosphate (cGMP) and guanylyl cyclase-stimulating vasodilators of large Ca2+-activated K+ channels (BK(Ca)) in human glomerular mesangial cells (MC). In cell-attached patches, with physiological NaCl bathing solutions, BK(Ca) was activated transiently by nitroprusside [NP; a nitric oxide (NO) donor], atrial natriuretic peptide (ANP), and dibutyryl cGMP (DBcGMP), reaching peak responses between 10 and 60 s and decreasing to near baseline activity within the next 120 s. In the presence of LY-83583, a specific inhibitor of guanylyl cyclase, BK(Ca) was activated on cell by DBcGMP but not by NP or ANP. In all cases, the increase in channel activity coincided with a decrease in channel amplitude, indicating that the membrane potential was approaching equilibrium potential as BK(Ca) was activated. If membrane potential was maintained depolarized with 140 mM KCl in the bathing solution, DBcGMP induced a sustained activation of BK(Ca). In the continued presence of DBcGMP, BK(Ca) was further activated when 100 nM angiotensin II (ANG II) was added to the bathing solution. Experiments were performed to determine the role of BK(Ca) in the regulation by vasorelaxants of mesangial contraction measured as percent maximal and defined by reduction in length induced by replacing 135 mM bath NaCl with KCl. Contraction by ANG II (100 nM = 60.5%) was attenuated by NP (100 μM), ANP (1.0 μM), and DBcGMP (10 μM) in the absence, but not the presence, of iberiotoxin, a specific inhibitor of BK(Ca). These results indicate that guanylyl cyclase-stimulating vasorelaxants counteract ANG II-induced contraction of MC, in part, by repolarizing the membrane through activation of BK(Ca) channels.

Original languageEnglish (US)
Pages (from-to)C1773-C1779
JournalAmerican Journal of Physiology - Cell Physiology
Volume270
Issue number6 39-6
DOIs
StatePublished - Jun 1996

Keywords

  • angiotensin II
  • atrial natriuretic peptide
  • charybdotoxin
  • guanosine 3',5'-cyclic monophosphate
  • guanylyl cyclase
  • iberiotoxin
  • nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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