Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of KCa channels

Valerie A. Porter, Michael T. Rhodes, Helen L. Reeve, David N. Cornfield
2001 American Journal of Physiology - Lung cellular and Molecular Physiology  
Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of KCa channels. Am J Physiol Lung Cell Mol Physiol 281: L1379-L1385, 2001.-O2 sensing in fetal pulmonary artery smooth muscle is critically important in the successful transition to air breathing at birth. However, the mechanism by which the fetal pulmonary vasculature senses and responds to an acute increase in O2 tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in
more » ... lls were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mmHg). These cells showed a 25.1 Ϯ 1.7% decrease in intracellular calcium in response to an acute increase in O2 tension. Low concentrations of caffeine (0.5 mM) and diltiazem also decreased intracellular calcium. The decrease in intracellular calcium concentration in response to increasing O2 was inhibited by iberiotoxin and ryanodine. Freshly isolated fetal pulmonary artery smooth muscle cells exhibited "spontaneous transient outward currents," indicative of intracellular calcium spark activation of calciumsensitive potassium channels. The frequency of spontaneous transient outward currents increased when O2 tension was increased to normoxic levels. Increasing fetal pulmonary O 2 tension in acutely instrumented fetal sheep increased fetal pulmonary blood flow. Ryanodine attenuated O 2-induced pulmonary vasodilation. This study demonstrates that fetal pulmonary vascular smooth muscle cells are capable of responding to an acute increase in O2 tension and that this O2 response is mediated by intracellular calcium activation of calcium-sensitive potassium channels. smooth muscle cells; spontaneous transient outward current; calcium-sensitive potassium channel Address for reprint requests and other correspondence: V. A. Porter,
doi:10.1152/ajplung.2001.281.6.l1379 pmid:11704533 fatcat:qhpauls2pnbitprrpy3a6jqtl4