Functional characterization of voltage-gated K+ channels in mouse pulmonary artery smooth muscle cells

Eun A. Ko, Elyssa D. Burg, Oleksandr Platoshyn, Joseph Msefya, Amy L. Firth, Jason X.J. Yuan

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Mice are useful animal models to study pathogenic mechanisms involved in pulmonary vascular disease. Altered expression and function of voltage-gated K+ (KV) channels in pulmonary artery smooth muscle cells (PASMCs) have been implicated in the development of pulmonary arterial hypertension. KV currents (IK(V)) in mouse PASMCs have not been comprehensively characterized. The main focus of this study was to determine the biophysical and pharmacological properties of IK(V) in freshly dissociated mouse PASMCs with the patch-clamp technique. Three distinct whole cell IK(V) were identified based on the kinetics of activation and inactivation: rapidly activating and noninactivating currents (in 58% of the cells tested), rapidly activating and slowly inactivating currents (23%), and slowly activating and noninactivating currents (17%). Of the cells that demonstrated the rapidly activating noninactivating current, 69% showed I K(V) inhibition with 4-aminopyridine (4-AP), while 31% were unaffected. Whole cell IK(V) were very sensitive to tetraethylammonium (TEA), as 1 mM TEA decreased the current amplitude by 32% while it took 10 mM 4-AP to decrease IK(V) by a similar amount (37%). Contribution of Ca2+-activated K+ (KCa) channels to whole cell IK(V) was minimal, as neither pharmacological inhibition with charybdotoxin or iberiotoxin nor perfusion with Ca 2+-free solution had an effect on the whole cell IK(V). Steady-state activation and inactivation curves revealed a window K+ current between -40 and -10 mV with a peak at -31.5 mV. Single-channel recordings revealed large-, intermediate-, and small-amplitude currents, with an averaged slope conductance of 119.4 ± 2.7, 79.8 ± 2.8, 46.0 ± 2.2, and 23.6 ± 0.6 pS, respectively. These studies provide detailed electrophysiological and pharmacological profiles of the native K V currents in mouse PASMCs.

Original languageEnglish (US)
Pages (from-to)C928-C937
JournalAmerican Journal of Physiology - Cell Physiology
Volume293
Issue number3
DOIs
StatePublished - Sep 2007

Keywords

  • K channels

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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