Hypoxia modulates cyclic AMP activation of BKCa channels in rat pulmonary arterial smooth muscle

Scott A. Barman, Shu Zhu, Richard E. White

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The signal transduction mechanisms defining the role of cyclic nucleotides in the regulation of potassium channel activity in pulmonary vascular smooth muscle are currently an area of great interest. Normally, signaling mechanisms that elevate cyclic AMP (cAMP) open potassium channels. Modulation of the large-conductance, calcium- and voltage-activated potassium (BKCa) channel is important in the regulation of pulmonary arterial pressure, and inhibition (closing) of the BKCa channel has been implicated in the development of pulmonary vasoconstriction. Accordingly, studies were done to determine the effect of cAMP-elevating agents on BKCa channel activity under normoxic and hypoxic conditions using patch-clamp studies in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR). Forskolin (10 μM; n = 4), a stimulator of adenylate cyclase and an activator of cAMP-dependent protein kinase (PKA), and CPT-cAMP (100 μM; n = 3), a membrane-permeable derivative of cAMP, opened BKCa channels in single FHR PASMC under normoxic conditions. Exposure of FHRs to 4 weeks of 10% O 2 (hypoxia) significantly attenuated the effect of both forskolin (n = 7) and CPT-cAMP (n = 14) on BKCa channel activity in PASMC. These results suggest that this phenomenon may serve as a physiological mechanism to cause hypoxic vasoconstriction in the pulmonary circulation via modulation of BKCa channels.

Original languageEnglish (US)
Pages (from-to)353-361
Number of pages9
JournalLung
Volume183
Issue number5
DOIs
StatePublished - Oct 2005

Keywords

  • BK channels
  • Cyclic AMP
  • Forskolin
  • Hypoxia
  • Pulmonary arterial smooth muscle

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'Hypoxia modulates cyclic AMP activation of BK<sub>Ca</sub> channels in rat pulmonary arterial smooth muscle'. Together they form a unique fingerprint.

  • Cite this