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Am J Physiol Lung Cell Mol Physiol (March 26, 2004). doi:10.1152/ajplung.00438.2003
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Submitted on December 9, 2003
Accepted on March 19, 2004

Functional voltage-dependent K+ channels in human pulmonary artery smooth muscle cells

Oleksandr Platoshyn1, Carmelle V. Remillard1, Ivana Fantozzi1, Mehran Mandegar1, Tiffany T. Sison1, Shen Zhang1, Elyssa Burg1, and Jason X.-J Yuan1*

1 Department of Medicine, University of California, San Diego, San Diego, California, USA

* To whom correspondence should be addressed. E-mail: xiyuan{at}ucsd.edu.

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 bathed in Ca2+-free solutions based on the kinetics of current activation and inactivation. Using RT-PCR, we detected transcripts of a) twenty-two 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), b) three KV channel {beta} subunits (KV{beta}1-3), c) four KCa channel {alpha} subunits (Slo-{alpha}1, and SK2-SK4), and d) 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.




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