Pulmonary vascular response to normoxia and K-Ca channel activity is developmentally regulated

To address developmental regulation of pulmonary vascular O-2 sensing, we t ested the hypotheses that 1) fetal but not adult pulmonary artery smooth mu scle cells (PASMCs) can directly sense an acute increase in O-2, 2) Ca2+-se nsitive K+ (K-Ca) channel activity decreases with maturation, and 3) PASMC K-Ca channel expression decreases with maturation. We used fluorescence mic roscopy to confirm that fetal but not adult PASMCs are able to sense an acu te increase in O-2 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) ca used 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 p ulmonary arteries from fetal and adult sheep were examined. Both K-Ca chann el protein and mRNA expression in the distal pulmonary vasculature decrease d with maturation. We conclude that maturation-dependent changes in PASMC O -2 sensing render the fetal PASMCs uniquely sensitive to an acute increase in O-2 tension at a biologically critical time point.