Voltage-gated K+ currents regulate resting membrane potential and [Ca2+](i) in pulmonary arterial myocytes

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Abstract

The membrane potential (E(m)) 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 mildly permeable to K+; thus, the resting E(m) is controlled by K permeability through sarcolemmal K+ channels. At least three K+ currents, voltage-gated K+ (K(v)) currents, Ca2+ activated K+ (K(Ca)) currents, and ATP-sensitive (K(ATP)) 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 (K(v), K(Ca), and/or K(ATP)) is responsible for controlling E(m) 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 K(Ca) and K(v) currents. Removal of extracellular Ca2+ and increase of intracellular EGTA concentration (to 10 mmol/L) eliminated the Ca2+ influx-dependent K(Ca) current. 4-Aminopyridine (4-AP, 5 to 10 mmol/L) but not charybdotoxin (ChTX, 10 to 20 nmol/L) significantly reduced K(v) current under these conditions. In current clump experiments, 4-AP decreased E(m), (depolarization) and induced Ca2+-dependent action potentials; this depolarization increased [Ca2+](i) in intact PASMCs. Neither ChTX nor the specific blocker of K(ATP), 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 K(v) currents that are active in the resting state are the major contributors to regulation of E(m) and thus [Ca2+](i) in rat PASMCs.

Original languageEnglish (US)
Pages (from-to)370-378
Number of pages9
JournalCirculation research
Volume77
Issue number2
StatePublished - Aug 1 1995

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Keywords

  • ATP-sensitive K channels
  • Ca-activated K channels
  • intracellular Ca
  • membrane potential
  • voltage-gated K channels

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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