Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of K(Ca) channels.
O(2) 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 O(2) tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mmHg). These cells showed a 25.1 +/- 1.7% decrease in intracellular calcium in response to an acute increase in O(2) tension. Low concentrations of caffeine (0.5 mM) and diltiazem also decreased intracellular calcium. The decrease in intracellular calcium concentration in response to increasing O(2) 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 calcium-sensitive potassium channels. The frequency of spontaneous transient outward currents increased when O(2) 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 O(2) tension and that this O(2) response is mediated by intracellular calcium activation of calcium-sensitive potassium channels.
Porter
V A
VA
Division of Pediatric Pulmonology and Critical Care Medicine, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA. porte030@tc.umn.edu
Rhodes
M T
MT
Reeve
H L
HL
Cornfield
D N
DN
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D005333:Fetus / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects*
D024681:Potassium Channels, Calcium-Activated; D012433:Ryanodine; D011188:Potassium; D010100:Oxygen; D002118:Calcium