Faculty Collaboration Database

Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy. Am J Physiol Lung Cell Mol Physiol 2012 Jan 01;302(1):L120-32

Date

10/04/2011

Pubmed ID

21964407

Pubmed Central ID

PMC3349372

DOI

10.1152/ajplung.00194.2011

Scopus ID

2-s2.0-83755196214 (requires institutional sign-in at Scopus site)   56 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 (qRT-PCR), 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.

Author List

Brueggemann LI, Kakad PP, Love RB, Solway J, Dowell ML, Cribbs LL, Byron KL

MESH terms used to index this publication - Major topics in bold

Aminopyridines
Animals
Anthracenes
Bronchoconstriction
Bronchodilator Agents
Calcium Channel Blockers
Carbamates
Celecoxib
Guinea Pigs
Histamine
Humans
KCNQ Potassium Channels
Male
Methacholine Chloride
Myocytes, Smooth Muscle
Patch-Clamp Techniques
Phenylenediamines
Pyrazoles
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Sulfonamides
Verapamil