Inhibition of inwardly rectifying K+ channels by cGMP in pulmonary vascular endothelial cells

Research output: Contribution to journalArticle

Abstract

Endothelial barrier dysfunction is typically triggered by increased intracellular Ca2+ concentration. Membrane-permeable analogs of guanosine 3′,5′-cyclic monophosphate (cGMP) prevent disruption of endothelial cell integrity. Because membrane potential (Em), which influences the electrochemical gradient for Ca2+ influx, is regulated by K+ channels, we investigated the effect of 8-bromo-cGMP on Em and inwardly rectifying K+ (KIR) currents in bovine pulmonary artery and microvascular endothelial cells (BPAEC and BMVEC), using whole cell patch-clamp techniques. Both cell types exhibited inward currents at potentials negative to -50 mV that were abolished by application of 10 μM Ba2+, consistent with KIR current. Ba2+ also depolarized both cell types. 8-Bromo-cGMP (10-3 M) depolarized BPAEC and BMVEC and inhibited KIR current. Pretreatment with Rp-8-cPCT-cGMPS or KT-5823, protein kinase G (PKG) antagonists, did not prevent current inhibition by 8-bromo-cGMP. These data suggest that 8-bromo-cGMP induces depolarization in BPAEC and BMVEC due, in part, to PKG-independent inhibition of KIR current. The depolarization could be a protective mechanism that prevents endothelial cell barrier dysfunction by reducing the driving force for Ca2+ entry.

Original languageEnglish (US)
Pages (from-to)L297-L304
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume283
Issue number2 27-2
StatePublished - Aug 3 2002

Keywords

  • Ion channels
  • Membrane potential
  • Protein kinase G

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Fingerprint Dive into the research topics of 'Inhibition of inwardly rectifying K+ channels by cGMP in pulmonary vascular endothelial cells'. Together they form a unique fingerprint.

  • Cite this