Voltage-gated K+-channel activity in ovine pulmonary vasculature is developmentally regulated

To examine mechanisms underlying developmental changes in pulmonary vascula r tone, we tested the hypotheses that 1) maturation-related changes in the ability of the pulmonary vasculature to respond to hypoxia are intrinsic to the pulmonary artery (PA) smooth muscle cells (SMCs); 2) voltage-gated K(K-v)-channel activity increases with maturation; and 3) O-2-sensitive Kv2. 1 channel expression and message increase with maturation. To confirm that maturational differences are intrinsic to PASMCs, we used fluorescence micr oscopy to study the effect of acute hypoxia on cytosolic Ca2+ concentration ([Ca2+](i)) in SMCs isolated from adult and fetal PAs. Although PASMCs fro m both fetal and adult circulations were able to sense an acute decrease in O-2 tension, acute hypoxia induced a more rapid and greater change in [Ca2 +](i) in magnitude in PASMCs from adult compared with fetal PAs. To determi ne developmental changes in K-v-channel activity, the effects of the K+-cha nnel antagonist 4-aminopyridine (4-AP) were studied on fetal and adult PASM C [Ca2+](i). 4-AP (1 mM) caused PASMC [Ca2+](i) to increase by 94 +/- 22% i n the fetus and 303 +/- 46% in the adult. K-v-channel expression and mRNA l evels in distal pulmonary arteries from fetal, neonatal, and adult sheep we re determined through the use of immunoblotting and semiquantitative RT-PCR . Both Kv2.1-channel protein and mRNA expression in distal pulmonary vascul ature increased with maturation. We conclude that there are maturation-depe ndent changes in PASMC O-2 sensing that may render the adult PASMCs more re sponsive to acute hypoxia.