A maturational shift in pulmonary K+ channels, from Ca2+ sensitive to voltage dependent.
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 microM; 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.
Reeve
H L
HL
Department of Physiology, University of Minnesota, Minneapolis 55455, Minnesota, USA.
Weir
E K
EK
Archer
S L
SL
Cornfield
D N
DN
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004594:Electrophysiology; D005333:Fetus / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology; D008564:Membrane Potentials / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D012756:Sheep / Q000196:embryology
D015221:Potassium Channels; D002118:Calcium