Diversity of voltage-dependent K+ channels in human pulmonary artery smooth muscle cells.
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(+) (K(V)) currents and Ca(2+)-activated K(+) (K(Ca)) currents were observed and characterized. In cell-attached patches of PASMC bathed in Ca(2+)-containing solutions, depolarization elicited a wide range of K(+) unitary conductances (6-290 pS). When cells were dialyzed with Ca(2+)-free and K(+)-containing solutions, depolarization elicited four components of K(V) currents in PASMC based on the kinetics of current activation and inactivation. Using RT-PCR, we detected transcripts of 1) 22 K(V) channel alpha-subunits (K(V)1.1-1.7, K(V)1.10, K(V)2.1, K(V)3.1, K(V)3.3-3.4, K(V)4.1-4.2, K(V)5.1, K(V) 6.1-6.3, K(V)9.1, K(V)9.3, K(V)10.1, and K(V)11.1), 2) three K(V) channel beta-subunits (K(V)beta 1-3), 3) four K(Ca) channel alpha-subunits (Slo-alpha 1 and SK2-SK4), and 4) four K(Ca) channel beta-subunits (K(Ca)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 Ca(2+), and pulmonary vasomotor tone.
Platoshyn
Oleksandr
O
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Diego, 92103, USA.
Remillard
Carmelle V
CV
Fantozzi
Ivana
I
Mandegar
Mehran
M
Sison
Tiffany T
TT
Zhang
Shen
S
Burg
Elyssa
E
Yuan
Jason X-J
JX
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004553:Electric Conductivity; D004594:Electrophysiology; D015870:Gene Expression; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009994:Osmolar Concentration; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism* / Q000502:physiology
D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D002118:Calcium