Hypoxia inhibits gene expression of voltage-gated K+ channel α subunits in pulmonary artery smooth muscle cells

Jian Wang, Magdalena Juhaszova, Lewis J. Rubin, Xiao Jian Yuan

Research output: Contribution to journalArticle

217 Scopus citations

Abstract

Activity of voltage-gated K+ channels (K(V)) in pulmonary arterial smooth muscle cells (PASMC) is pivotal in controlling membrane potential, cytoplasmic free Ca2+ concentration ([Ca2+)(cyt)), and pulmonary vasomotor tone. Acute hypoxia selectively inhibits K(V) channels, depolarizes PASMC, raises [Ca2+](cyt), and causes pulmonary vasoconstriction and vascular remodeling. Prolonged hypoxia (24-60 h) decreased significantly the mRNA levels of K(V) channel α subunits, K(V)1.2 and K(V)1.5. Consistently, the protein levels of K(V)1.2 and K(V)1.5 were also decreased significantly by hypoxia (48-72 h). Nevertheless, hypoxia affected negligibly the mRNA levels of K(V) channel β subunits (K(V)β1, K(V)β2, and K(V)β3). The native K+ channels are composed of pore-forming α and auxiliary β subunits. Assembly of K(V) β subunits with α subunits confers rapid inactivation on the slowly or non-inactivating delayed rectifier K(V) channels. K(V) β subunits also function as an open-channel blocker of K(V) channels. Thus, the diminished transcription and expression of K(V) a subunits may reduce the number of K(V) channels and decrease K(V) currents. Unchanged transcription of K(V) β subunits may increase the fraction of the K(V) channel α subunits that are associated with β subunits and further reduce the total K(V) currents. These data demonstrate a novel mechanism by which chronic hypoxia may cause pulmonary vasoconstriction and hypertension.

Original languageEnglish (US)
Pages (from-to)2347-2353
Number of pages7
JournalJournal of Clinical Investigation
Volume100
Issue number9
DOIs
StatePublished - Nov 1 1997
Externally publishedYes

Keywords

  • K(V)1.2
  • K(V)1.5
  • Reverse transcription- PCR
  • Western blotting
  • α subunits
  • β subunits

ASJC Scopus subject areas

  • Medicine(all)

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