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Am J Physiol Lung Cell Mol Physiol 274: L621-L635, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 4, L621-L635, April 1998

Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells

Xiao-Jian Yuan1,2, Jian Wang1, Magdalena Juhaszova2, Vera A. Golovina2, and Lewis J. Rubin1,2

1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, and 2 Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201

K+-channel activity-mediated alteration of the membrane potential and cytoplasmic free Ca2+ concentration ([Ca2+]cyt) is a pivotal mechanism in controlling pulmonary vasomotor tone. By using combined approaches of patch clamp, imaging fluorescent microscopy, and molecular biology, we examined the electrophysiological properties of K+ channels and the role of different K+ currents in regulating [Ca2+]cyt and explored the molecular identification of voltage-gated K+ (KV)- and Ca2+-activated K+ (KCa)-channel genes expressed in pulmonary arterial smooth muscle cells (PASMC). Two kinetically distinct KV currents [IK(V)], a rapidly inactivating (A-type) and a noninactivating delayed rectifier, as well as a slowly activated KCa current [IK(Ca)] were identified. IK(V) was reversibly inhibited by 4-aminopyridine (5 mM), whereas IK(Ca) was significantly inhibited by charybdotoxin (10-20 nM). K+ channels are composed of pore-forming alpha -subunits and auxiliary beta -subunits. Five KV-channel alpha -subunit genes from the Shaker subfamily (KV1.1, KV1.2, KV1.4, KV1.5, and KV1.6), a KV-channel alpha -subunit gene from the Shab subfamily (KV2.1), a KV-channel modulatory alpha -subunit (KV9.3), and a KCa-channel alpha -subunit gene (rSlo), as well as three KV-channel beta -subunit genes (KVbeta 1.1, KVbeta 2, and KVbeta 3) are expressed in PASMC. The data suggest that 1) native K+ channels in PASMC are encoded by multiple genes; 2) the delayed rectifier IK(V) may be generated by the KV1.1, KV1.2, KV1.5, KV1.6, KV2.1, and/or KV2.1/KV9.3 channels; 3) the A-type IK(V) may be generated by the KV1.4 channel and/or the delayed rectifier KV channels (KV1 subfamily) associated with beta -subunits; and 4) the IK(Ca) may be generated by the rSlo gene product. The function of the KV channels plays an important role in the regulation of membrane potential and [Ca2+]cyt in PASMC.

potassium channel; polymerase chain reaction; fluorescence microscopy; patch clamp; cytoplasmic calcium


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