Kv7 potassium channels in airway smooth muscle cells:signal transduction intermediates and pharmacological targets for bronchodilator therapy

Lioubov I. Brueggemann, Priyanka P. Kakad, Robert B. Love, Julian Solway, Maria L. Dowell, Leanne L. Cribbs, Kenneth L. Byron

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Expression and function of Kv7 (KCNQ) voltage-activated potassium channels in guinea pig and human airway smooth muscle cells (ASMCs) were investigated by quantitative reverse transcriptase polymerase chain reaction (qRTPCR), patch-clamp electrophysiology, and precision-cut lung slices. qRT-PCR revealed expression of multiple KCNQ genes in both guinea pig and human ASMCs. Currents with electrophysiological and pharmacological characteristics of Kv7 currents were measured in freshly isolated guinea pig and human ASMCs. In guinea pig ASMCs, Kv7 currents were significantly suppressed by application of the bronchoconstrictor agonists methacholine (100 nM) or histamine (30 μM), but current amplitudes were restored by addition of a Kv7 channel activator, flupirtine (10 μM). Kv7 currents in guinea pig ASMCs were also significantly enhanced by another Kv7.2-7.5 channel activator, retigabine, and by celecoxib and 2,5-dimethyl celecoxib. In precision-cut human lung slices, constriction of airways by histamine was significantly reduced in the presence of flupirtine. Kv7 currents in both guinea pig and human ASMCs were inhibited by the Kv7 channel blocker XE991. In human lung slices, XE991 induced robust airway constriction, which was completely reversed by addition of the calcium channel blocker verapamil. These findings suggest that Kv7 channels in ASMCs play an essential role in the regulation of airway diameter and may be targeted pharmacologically to relieve airway hyperconstriction induced by elevated concentrations of bronchoconstrictor agonists.

Original languageEnglish (US)
Pages (from-to)L120-L132
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume302
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Asthma therapy
  • Bronchoconstrictor signal transduction
  • Kcnq voltage-activated potassium channel
  • Precision-cut lung slice

ASJC Scopus subject areas

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

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