Properties of a novel potassium current that is active at resting potential in rabbit pulmonary artery smooth muscle cells

1. An outward current (I-K(N)) was identified in rabbit pulmonary artery myocytes, which persisted after Ca2+-activated and ATP-sensitive K+ currents were blocked by TEA (10 mM) and glibenclamide (10 mu M), respectively, and after A-like (I-K(A)) and delayed rectifier (I-K(V)) K+ currents were inactivated by clamping the cell at 0 mV for &gt;10 min. It was found in smooth muscle cells at all levels of the pulmonary arterial tree.2. The relationship between the reversal potential of I-K(N) and the extracellular K+ concentration ([K+](o)) was close to that expected for a K+-selective channel. Deviation from Nernstian behaviour at low [K+](o) could be accounted for by the presence of an accompanying leakage current.3. I-K(N) is voltage gated. It has a low threshold for activation, between -80 and -65 mV, and activates slowly without delay. Activation follows an exponential time course with a time constant of 1.6 s at -60 mV. Deactivation is an order of magnitude faster-than activation, with a time constant of 107 ms at -60 mV.4. I-K(N) showed a similar sensitivity to 4-aminopyridine as I-K(A) and I-K(V), with 49% inhibition at 10 mM. The current was not blocked by 10 mu M quinine, which did inhibit I-K(A) and I-K(V), by 51 and 47%, respectively.5. Activation of I-K(N) was detected at potentials close to the resting membrane potential of pulmonary artery smooth muscle cells, under physiological conditions. Thus it is likely to contribute to the resting membrane potential of these cells.</p

Properties of a novel potassium current that is active at resting potential in rabbit pulmonary artery smooth muscle cells

1. An outward current (I-K(N)) was identified in rabbit pulmonary artery myocytes, which persisted after Ca2+-activated and ATP-sensitive K+ currents were blocked by TEA (10 mM) and glibenclamide (10 mu M), respectively, and after A-like (I-K(A)) and delayed rectifier (I-K(V)) K+ currents were inactivated by clamping the cell at 0 mV for &gt;10 min. It was found in smooth muscle cells at all levels of the pulmonary arterial tree.2. The relationship between the reversal potential of I-K(N) and the extracellular K+ concentration ([K+](o)) was close to that expected for a K+-selective channel. Deviation from Nernstian behaviour at low [K+](o) could be accounted for by the presence of an accompanying leakage current.3. I-K(N) is voltage gated. It has a low threshold for activation, between -80 and -65 mV, and activates slowly without delay. Activation follows an exponential time course with a time constant of 1.6 s at -60 mV. Deactivation is an order of magnitude faster-than activation, with a time constant of 107 ms at -60 mV.4. I-K(N) showed a similar sensitivity to 4-aminopyridine as I-K(A) and I-K(V), with 49% inhibition at 10 mM. The current was not blocked by 10 mu M quinine, which did inhibit I-K(A) and I-K(V), by 51 and 47%, respectively.5. Activation of I-K(N) was detected at potentials close to the resting membrane potential of pulmonary artery smooth muscle cells, under physiological conditions. Thus it is likely to contribute to the resting membrane potential of these cells.</p

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

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 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.</p