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

Publisher Website
Google Scholar
Abstract
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+]cytand 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 KVcurrents [ IK(V)], a rapidly inactivating (A-type) and a noninactivating delayed rectifier, as well as a slowly activated KCacurrent [ 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 α-subunits and auxiliary β-subunits. Five KV-channel α-subunit genes from the Shaker subfamily (KV1.1, KV1.2, KV1.4, KV1.5, and KV1.6), a KV-channel α-subunit gene from the Shab subfamily (KV2.1), a KV-channel modulatory α-subunit (KV9.3), and a KCa-channel α-subunit gene ( rSlo), as well as three KV-channel β-subunit genes (KVβ1.1, KVβ2, and KVβ3) 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 KVchannels (KV1 subfamily) associated with β-subunits; and 4) the IK(Ca)may be generated by the rSlo gene product. The function of the KVchannels plays an important role in the regulation of membrane potential and [Ca2+]cytin PASMC.