Effect of normoxia and hypoxia on K+ current and resting membrane potential of fetal rabbit pulmonary artery smooth muscle

Z. Hong, E. K. Weir, A. Varghese, A. Olschewski

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

At birth, the increase in O2 tension (pO2) is an important cause of the decrease in pulmonary vascular resistance. In adult animals there are impressive interspecies differences in the level of hypoxia required to elicit a pulmonary vasoconstrictor response and in the amplitude of the response. Hypoxic inhibition of some potassium (K+) channels in the membrane of pulmonary arterial smooth muscle cells (PASMCs) helps to initiate hypoxic pulmonary vasoconstriction. To determine the effect of the change in pO2 on fetal rabbit PASMCs and to investigate possible species-dependent differences, we measured the current-voltage relationship and the resting membrane potential, in PASMCs from fetal resistance arteries using the amphotericin-perforated patch-clamp technique under hypoxic and normoxic conditions. Under hypoxic conditions, the K+ current in PASMCs was small, and could be inhibited by 4-aminopyridine, iberiotoxin and glibenclamide, reflecting contributions by Kv, KCa and KATP channels. The average resting membrane potential was -44.3±1.3 mV (n=29) and could be depolarized by 4-AP (5 mM) and ITX (100 nM) but not by glibenclamide (10 μM). Changing from hypoxia, that mimicked fetal life, to normoxia dramatically increased the KCa and consequently hyperpolarized (-9.3±1.7 mV; n=8) fetal rabbit PASMCs. Under normoxic conditions K + current was reduced by 4-AP with a significant change in resting membrane potential (11.1±1.7 mV; n=8). We conclude that resting membrane potential in fetal rabbit PASMCs under both hypoxic and normoxic conditions depends on both Kv and KCa channels, in contrast to fetal lamb or porcine PASMCs. Potential species differences in the K+ channels that control resting membrane potential must be taken into consideration in the interpretation of studies of neonatal pulmonary vascular reactivity to changes in O2 tension.

Original languageEnglish (US)
Pages (from-to)175-184
Number of pages10
JournalPhysiological Research
Volume54
Issue number2
StatePublished - 2005

Keywords

  • Electrophysiology
  • Fetal pulmonary artery smooth muscle
  • Hypoxic pulmonary vasoconstriction
  • Ion channels
  • Oxygen
  • Patch-clamp

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