A maturational shift in pulmonary K+ channels, from Ca2+ sensitive to voltage dependent

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

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


The mechanism responsible for the abrupt decrease in resistance of the pulmonary circulation at birth may include changes in the activity of O2- 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 Ca2+-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 Ca2+ 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 Ca2+-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)
Pages (from-to)L1019-L1025
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6 19-6
StatePublished - 1998


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


Dive into the research topics of 'A maturational shift in pulmonary K+ channels, from Ca2+ sensitive to voltage dependent'. Together they form a unique fingerprint.

Cite this