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

8 Citations (Scopus)

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 1 2005

Fingerprint

Cyclic AMP
Smooth Muscle
Lung
Potassium Channels
Smooth Muscle Myocytes
Colforsin
Vasoconstriction
Pulmonary Circulation
Cyclic Nucleotides
Cyclic AMP-Dependent Protein Kinases
Vascular Smooth Muscle
Adenylyl Cyclases
Hypoxia
Signal Transduction
Arterial Pressure
Calcium
Membranes

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology

Cite this

Hypoxia modulates cyclic AMP activation of BKCa channels in rat pulmonary arterial smooth muscle. / Barman, Scott A; Zhu, Shu; White, Richard E.

In: Lung, Vol. 183, No. 5, 01.10.2005, p. 353-361.

Research output: Contribution to journalArticle

Barman, Scott A ; Zhu, Shu ; White, Richard E. / Hypoxia modulates cyclic AMP activation of BKCa channels in rat pulmonary arterial smooth muscle. In: Lung. 2005 ; Vol. 183, No. 5. pp. 353-361.
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