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Am J Physiol Lung Cell Mol Physiol 287: L226-L238, 2004. First published March 26, 2004; doi:10.1152/ajplung.00438.2003
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Diversity of voltage-dependent K+ channels in human pulmonary artery smooth muscle cells

Oleksandr Platoshyn,* Carmelle V. Remillard,* Ivana Fantozzi, Mehran Mandegar, Tiffany T. Sison, Shen Zhang, Elyssa Burg, and Jason X.-J. Yuan

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Diego, California 92103

Submitted 9 December 2003 ; accepted in final form 19 March 2004

Electrical excitability, which plays an important role in excitation-contraction coupling in the pulmonary vasculature, is regulated by transmembrane ion flux in pulmonary artery smooth muscle cells (PASMC). This study examined the heterogeneous nature of native voltage-dependent K+ channels in human PASMC. Both voltage-gated K+ (KV) currents and Ca2+-activated K+ (KCa) currents were observed and characterized. In cell-attached patches of PASMC bathed in Ca2+-containing solutions, depolarization elicited a wide range of K+ unitary conductances (6–290 pS). When cells were dialyzed with Ca2+-free and K+-containing solutions, depolarization elicited four components of KV currents in PASMC based on the kinetics of current activation and inactivation. Using RT-PCR, we detected transcripts of 1) 22 KV channel {alpha}-subunits (KV1.1–1.7, KV1.10, KV2.1, KV3.1, KV3.3–3.4, KV4.1–4.2, KV5.1, KV 6.1–6.3, KV9.1, KV9.3, KV10.1, and KV11.1), 2) three KV channel {beta}-subunits (KV{beta}1–3), 3) four KCa channel {alpha}-subunits (Slo-{alpha}1 and SK2–SK4), and 4) four KCa channel {beta}-subunits (KCa{beta}1–4). Our results show that human PASMC exhibit a variety of voltage-dependent K+ currents with variable kinetics and conductances, which may result from various unique combinations of {alpha}- and {beta}-subunits forming the native channels. Functional expression of these channels plays a critical role in the regulation of membrane potential, cytoplasmic Ca2+, and pulmonary vasomotor tone.

membrane potential; calcium; proliferation; heterogeneity; calcium-activated potassium channel


Address for reprint requests and other correspondence: J. X.-J. Yuan, Div. of Pulmonary and Critical Care Medicine, UCSD Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8382 (E-mail: xiyuan{at}ucsd.edu).




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