Resting potentials and potassium currents during development of pulmonary artery smooth muscle cells

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 275; no. 3; pp. H887 - H899
• Main Authors: Evans, A. M, Osipenko, O. N, Haworth, S. G, Gurney, A. M
• Format: Journal Article
• Language: English
• Published: United States 01.09.1998
• Subjects: Aging; Animals; Animals, Newborn - growth & development; Calcium - pharmacology; Electric Conductivity; Glyburide - pharmacology; Hypoxia - physiopathology; Membrane Potentials; Muscle Development; Muscle, Smooth, Vascular - growth & development; Potassium Channels - drug effects; Potassium Channels - physiology; Pulmonary Artery - growth & development; Swine
• ISSN: 0363-6135; 0002-9513; 1522-1539
• DOI: 10.1152/ajpheart.1998.275.3.h887

1  University Department of Pharmacology, Oxford OX1 3QT; 2  Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1XW; and 3  Unit of Vascular Biology and Pharmacology, Institute of Child Health, London WC1 1EH, United Kingdom 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 O 2 -induced vasodilation in the fetus, channel inhibition being thought to promote Ca 2+ 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 Ca 2+ -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. newborn pig; pulmonary artery remodeling; porcine pulmonary artery; hypoxia