Pulmonary vascular response to normoxia and K_Ca channel activity is developmentally regulated

To address developmental regulation of pulmonary vascular O₂ sensing, we tested the hypotheses that 1) fetal but not adult pulmonary artery smooth muscle cells (PASMCs) can directly sense an acute increase in O₂, 2) Ca²⁺-sensitive K⁺ (K_Ca) channel activity decreases with maturation, and 3) PASMC K_Ca channel expression decreases with maturation. We used fluorescence microscopy to confirm that fetal but not adult PASMCs are able to sense an acute increase in O₂ tension. Acute normoxia induced a 22 ± 2% decrease in cytosolic Ca²⁺ concentration ([Ca²⁺]_i) in fetal PASMCs and no change in [Ca²⁺]_i in adult PASMCs (P < 0.01). The effects of K⁺ channel antagonists were studied on fetal and adult PASMC [Ca²⁺]_i. Iberiotoxin (10^-9 M) caused PASMC [Ca²⁺]_i to increase by 694 ± 22% in the fetus and caused no change in adult PASMCs. K_Ca channel expression and mRNA levels in distal pulmonary arteries from fetal and adult sheep were examined. Both K_Ca channel protein and mRNA expression in the distal pulmonary vasculature decreased with maturation. We conclude that maturation-dependent changes in PASMC O₂ sensing render the fetal PASMCs uniquely sensitive to an acute increase in O₂ tension at a biologically critical time point.