© 1995 American Heart Association, Inc.
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Voltage-Gated K+ Currents Regulate Resting Membrane Potential and [Ca2+]i in Pulmonary Arterial Myocytes
From the Department of Medicine, Division of Pulmonary and Critical Care Medicine, and the Department of Physiology, University of Maryland School of Medicine, Baltimore.
Correspondence to X.-Jian Yuan, MD, PhD, Pulmonary Division, UMAB Medical School, 10 S Pine St, Suite 800, Baltimore, MD 21201.
Abstract The membrane potential (Em) of pulmonary arterial smooth muscle cells (PASMCs) regulates pulmonary arterial tone by controlling voltage-gated Ca2+ channel activity, which is a major contributor to [Ca2+]i. The resting membrane is mainly permeable to K+; thus, the resting Em is controlled by K+ permeability through sarcolemmal K+ channels. At least three K+ currents, voltage-gated K+ (KV) currents, Ca2+-activated K+ (KCa) currents, and ATP-sensitive (KATP) currents, have been identified in PASMCs. In this study, both patch-clamp and quantitative fluorescent microscopy techniques were used to determine which kind(s) of K+ channels (KV, KCa, and/or KATP) is responsible for controlling Em and [Ca2+]i under resting conditions in rat PASMCs. When the bath solution contained 1.8 mmol/L Ca2+ and the pipette solution included 0.1 mmol/L EGTA, depolarizations (-40 to +80 mV) elicited both KCa and KV currents. Removal of extracellular Ca2+ and increase of intracellular EGTA concentration (to 10 mmol/L) eliminated the Ca2+ influx–dependent KCa current. 4-Aminopyridine (4-AP, 5 to 10 mmol/L) but not charybdotoxin (ChTX, 10 to 20 nmol/L) significantly reduced KV current under these conditions. In current-clamp experiments, 4-AP decreased Em (depolarization) and induced Ca2+-dependent action potentials; this depolarization increased [Ca2+]i in intact PASMCs. Neither ChTX nor the specific blocker of KATP channels, glibenclamide (2 to 10 µmol/L), caused membrane depolarization and the increase in [Ca2+]i. However, pretreatment of PASMCs with ChTX enhanced the 4-AP–induced increase in [Ca2+]i. These results suggest that the 4-AP–sensitive KV currents that are active in the resting state are the major contributors to regulation of Em and thus [Ca2+]i in rat PASMCs.
Key Words: voltage-gated K+ channels • Ca2+-activated K+ channels • ATP-sensitive K+ channels • membrane potential • intracellular Ca2+
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