Hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells

Amy L. Firth, Oleksandr Platoshyn, Elena E. Brevnova, Elyssa D. Burg, Frank Powell, Gabriel H. Haddad, Jason X.J. Yuan

Research output: Chapter in Book/Report/Conference proceedingConference contribution

8 Scopus citations

Abstract

Acute hypoxia induces pulmonary vasoconstriction and chronic hypoxia causes pulmonary vascular remodeling characterized by significant vascular medial hypertrophy. Electromechanical and pharmacomechanical mechanisms are involved in regulating pulmonary vasomotor tone, while changes in cytosolic Ca2+ concentration ([Ca2+]cyt) are an important signal in regulating contraction and proliferation of pulmonary artery smooth muscle cells (PASMC). Hypoxia-induced increases in [Ca2+]cyt are, in part, mediated by selective inhibition of voltage-gated K+ (Kv) channels in PASMC. Kv1.5, encoded by the KCNA5 gene, is a Kv channel α subunit that forms functional homotetrameric and heterotetrameric Kv channels in PASMC. Activity of Kv channels contributes to the regulation of resting membrane potential. Overexpression of the human KCNA5 gene in rat PASMC and other cell types increases whole-cell Kv currents and causes membrane hyperpolarization. However, acute hypoxia only reduced Kv currents in KCNA5-transfected PASMC. These results provide compelling evidence that Kv1.5 is an important hypoxia-sensitive Kv channel in PASMC, contributing to regulation of membrane potential and intracellular Ca2+ homeostasis during hypoxia. This hypoxia-sensitive mechanism essential for inhibiting Kv1.5 channel activity is exclusively present in PASMC.

Original languageEnglish (US)
Title of host publicationHypoxia and Consequences From Molecule to Malady
PublisherBlackwell Publishing Inc.
Pages101-111
Number of pages11
ISBN (Print)9781573317733
DOIs
StatePublished - Jan 1 2009
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1177
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Hypoxic pulmonary vasoconstriction (HPV)
  • K channels
  • Membrane potential
  • Pulmonary artery smooth muscle cells (PASMC)
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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    Firth, A. L., Platoshyn, O., Brevnova, E. E., Burg, E. D., Powell, F., Haddad, G. H., & Yuan, J. X. J. (2009). Hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells. In Hypoxia and Consequences From Molecule to Malady (pp. 101-111). (Annals of the New York Academy of Sciences; Vol. 1177). Blackwell Publishing Inc.. https://doi.org/10.1111/j.1749-6632.2009.05040.x