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

The mechanism responsible for the abrupt decrease in resistance of the pulm onary circulation at birth may include changes in the activity of O-2-sensi tive K+ channels. We characterized the electrophysiological properties of f etal and adult ovine pulmonary arterial (PA) smooth muscle cells (SMCs) usi ng 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 p otential (RMP) was -36 +/- 3 mV and could be depolarized by charybdotoxin ( 100 nM) or tetraethylammonium chloride (5 mM; both blockers of Ca2+-depende nt K+ channels) but not by C-aminopyridine (4-AP; 1 mM; blocker of voltage- gated K+ channels) or glibenclamide (10 mu M; blocker of ATP-dependent K+ c hannels). In hypoxia, chelation of intracellular Ca2+ by 5 mM 1,2-bis(2-ami nophenoxy)ethane-N,N,N',N'-tetraacetic acid further reduced the amplitude o f the whole cell K+ current and prevented spontaneously transient outward c urrent activity. Under these conditions, the remaining current was partiall y inhibited by 1 mM 4-AP. K+ currents of fetal PASMCs maintained in normoxi a 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-se nsitive K+ currents were partially inhibited by exposure to acute hypoxia. We conclude that the K+ channel regulating RMP in the ovine pulmonary circu lation changes after birth from a Ca2+-dependent K+ channel to a voltage-de pendent K+ channel. The maturational-dependent differences in the mechanism of the response to acute hypoxia may be due to this difference in K+ chann els.