Resting potentials and potassium currents during development of pulmonary artery smooth muscle cells.
The pulmonary circulation changes rapidly at birth to adapt to extrauterine life. The neonate is at high risk of developing pulmonary hypertension, a common cause being perinatal hypoxia. Smooth muscle K+ channels have been implicated in hypoxic pulmonary vasoconstriction in adults and O2-induced vasodilation in the fetus, channel inhibition being thought to promote Ca2+ influx and contraction. We investigated the K+ currents and membrane potentials of pulmonary artery myocytes during development, in normal pigs and pigs exposed for 3 days to hypoxia, either from birth or from 3 days after birth. The main finding is that cells were depolarized at birth and hyperpolarized to the adult level of -40 mV within 3 days. Hypoxia prevented the hyperpolarization when present from birth and reversed it when present from the third postnatal day. The mechanism of hyperpolarization is unclear but may involve a noninactivating, voltage-gated K+ channel. It is not caused by increased Ca2+-activated or delayed rectifier current. These currents were small at birth compared with adults, declined further over the next 2 wk, and were suppressed by exposure to hypoxia from birth. Hyperpolarization could contribute to the fall in pulmonary vascular resistance at birth, whereas the low K+-current density, by enhancing membrane excitability, would contribute to the hyperreactivity of neonatal vessels. Hypoxia may hinder pulmonary artery adaptation by preventing hyperpolarization and suppressing K+ current.
University Department of Pharmacology, Oxford OX1 3QT, United Kingdom.
A M
AM
Evans
O N
ON
Osipenko
S G
SG
Haworth
A M
AM
Gurney
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D002118:Calcium / Q000494:pharmacology; D004553:Electric Conductivity; D005905:Glyburide / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D008564:Membrane Potentials; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000254:growth & development*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011651:Pulmonary Artery / Q000254:growth & development*; D013552:Swine
D015221:Potassium Channels; D005905:Glyburide; D002118:Calcium