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 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.