A maturational shift in pulmonary K + channels, from Ca 2+ sensitive to voltage dependent

Helen L. Reeve, E. Kenneth Weir, Stephen L. Archer, David N. Cornfield

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The mechanism responsible for the abrupt decrease in resistance of the pulmonary circulation at birth may include changes in the activity of O 2- sensitive K + channels. We characterized the electrophysiological properties of fetal and adult ovine pulmonary arterial (PA) smooth muscle cells (SMCs) using conventional and amphotericin B-perforated patch-clamp techniques. Whole cell K + currents of fetal PASMCs in hypoxia were small and characteristic of spontaneously transient outward currents. The average resting membrane potential (RMP) was -36 ± 3 mV and could be depolarized by charybdotoxin (100 nM) or tetraethylammonium chloride (5 mM; both blockers of Ca 2+-dependent K + channels) but not by 4-aminopyridine (4-AP; 1 mM; blocker of voltage-gated K + channels) or glibenclamide (10 μM; blocker of ATP-dependent K + channels). In hypoxia, chelation of intracellular Ca 2+ by 5 mM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid further reduced the amplitude of the whole cell K + current and prevented spontaneously transient outward current activity. Under these conditions, the remaining current was partially inhibited by 1 mM 4-AP. K + currents of fetal PASMCs maintained in normoxia were not significantly reduced by acute hypoxia. In normoxic adult PASMCs, whole cell K + currents were large and RMP was -49 ± 3 mV. These 4-AP-sensitive K + currents were partially inhibited by exposure to acute hypoxia. We conclude that the K + channel regulating RMP in the ovine pulmonary circulation changes after birth from a Ca 2+-dependent K + channel to a voltage-dependent K + channel. The maturational-dependent differences in the mechanism of the response to acute hypoxia may be due to this difference in K + channels.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number6 19-6
StatePublished - Dec 1 1998

Keywords

  • Adult
  • Fetus
  • Hypoxia
  • Ion channels
  • Pulmonary circulation

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