Am. Evans et al., RESTING POTENTIALS AND POTASSIUM CURRENTS DURING DEVELOPMENT OF PULMONARY-ARTERY SMOOTH-MUSCLE CELLS, American journal of physiology. Heart and circulatory physiology, 44(3), 1998, pp. 887-899
The pulmonary circulation changes rapidly at birth to adapt to extraut
erine life. The neonate is at high risk of developing pulmonary hypert
ension, a common cause being perinatal hypoxia. Smooth muscle K+ chann
els have been implicated in hypoxic pulmonary vasoconstriction in adul
ts and O-2-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, e
ither 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 postnat
al day. The mechanism of hyperpolarization is unclear but may involve
a noninactivating, voltage-gated K+ channel. It is not caused by incre
ased 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. Hyperpolar
ization could contribute to the fall in pulmonary vascular resistance
at birth, whereas the low K+-current density, by enhancing membrane ex
citability, would contribute to the hyperreactivity of neonatal vessel
s. Hypoxia may hinder pulmonary artery adaptation by preventing hyperp
olarization and suppressing K+ current.