期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 287, 期 1, 页码 L226-L238出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00438.2003
关键词
membrane potential; calcium; proliferation; heterogeneity; calcium-activated potassium channel
资金
- NHLBI NIH HHS [HL-54043, HL-66941, HL-66012, HL-69758, R01 HL066012, HL-64945] Funding Source: Medline
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 Ca2+-activated K+ (K-Ca) 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 (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)beta1-3), 3) four K-Ca channel alpha-subunits (Slo-alpha1 and SK2-SK4), and 4) four K-Ca channel beta-subunits (K(Ca)beta1-4). 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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