Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells

Xiao Jian Yuan, Jian Wang, Magdalena Juhaszova, Vera A. Golovina, Lewis J. Rubin

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

K+-channel activity-mediated alteration of the membrane potential and cytoplasmic free Ca2+ concentration ([Ca2+](cyt)) is a pivotal mechanism in controlling pulmonary vasomotor tone. By using combined approaches of patch clamp, imaging fluorescent microscopy, and molecular biology, we examined the electrophysiological properties of K+ channels and the role of different K+ currents in regulating [Ca2+](cyt) and explored the molecular identification of voltage-gated K+ (Kv)- and Ca2+-activated K+ (K(Ca))channel genes expressed in pulmonary arterial smooth muscle cells (PASMC). Two kinetically distinct K(V) currents [I(K(V))], a rapidly inactivating (A-type) and a noninactivating delayed rectifier, as well as a slowly activated K(Ca) current [I(K(Ca))] were identified. I(K(V)) was reversibly inhibited by 4-aminopyridine (5 mM), whereas I(K(Ca)) was significantly inhibited by charybdotoxin (10-20 nM). K+ channels are composed of pore-forming α-subunits and auxiliary β-subunits. Five K(V)channel α-subunit genes from the Shaker subfamily (K(V)1.1, K(V)l.2, K(V)l.4, K(V)l.5, and K(V)l.6), a K(V)-channel α-subunit gene from the Shab subfamily (K(V)2.1), a K(V)-channel modulatory α-subunit (K(V)9.3), and a K(Ca)-channel α-subunit gene (rSlo), as well as three K(V)-channel β- subunit genes (K(V)β1.1, K(V)β2, and K(V)β3) are expressed in PASMC. The data suggest that 1) native K+ channels in PASMC are encoded by multiple genes; 2) the delayed rectifier I(K(V)) may be generated by the K(V)l.1, K(V)l.2, K(V)l.5, K(V)l.6, K(V)2.1, and/or K(V)2.1/K(V)9.3 channels; 3) the A-type I(K(V)) may be generated by the K(V)l.4 channel and/or the delayed rectifier K(V) channels (K(V)l subfamily) associated with β-subunits; and 4) the I(K(Ca)) may be generated by the rSlo gene product. The function of the K(V) channels plays an important role in the regulation of membrane potential and [Ca2+](cyt) in PASMC.

Original languageEnglish (US)
Pages (from-to)L621-L635
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume274
Issue number4 18-4
StatePublished - Apr 1 1998
Externally publishedYes

Keywords

  • Cytoplasmic calcium
  • Fluorescence microscopy
  • Patch clamp
  • Polymerase chain reaction
  • Potassium channel

ASJC Scopus subject areas

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

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