Regulation of the resting potential of rabbit pulmonary artery myocytes by a low threshold, O2‐sensing potassium current*

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Abstract
The contributions of specific K+ currents to the resting membrane potential of rabbit isolated, pulmonary artery myocytes, and their modulation by hypoxia, were investigated by use of the whole‐cell, patch‐clamp technique. In the presence of 10 μm glibenclamide the resting potential (−50±4 mV, n=18) was unaffected by 10 μm tetraethylammonium ions, 200 nm charybdotoxin, 200 nm iberiotoxin, 100 μm ouabain or 100 μm digitoxin. The negative potential was therefore maintained without ATP‐sensitive (KATP) or large conductance Ca2+‐sensitive (BKCa) K channels, and without the Na+‐K+ATPase. The resting potential, the delayed rectifier current (IK(V)) and the A‐like K+ current (IK(A)) were all reduced in a concentration‐dependent manner by 4‐aminopyridine (4‐AP) and by quinine. 4‐AP was equally potent at reducing the resting potential and IK(V), 10 mm causing depolarization from −44 mV to −22 mV with accompanying inhibition of IK(V) by 56% and IK(A) by 79%. In marked contrast, the effects of quinine on resting potential were poorly correlated with its effects on both IK(A) and IK(V). At 10 mm, quinine reduced IK(V) and IK(A) by 47% and 38%, respectively, with no change in the resting potential. At 100 μm, both currents were almost abolished while the resting potential was reduced IK(A) or IK(V), but essentially abolished the resting potential. Reduction of the resting potential by quinine was correlated with inhibition of a voltage‐gated, low threshold, non‐inactivating K+ current, IK(N). Thus, 100 μm quinine reduced both IK(N) and the resting potential by around 50%. The resting membrane potential was the same whether measured after clamping the cell at −80 mV, or immediately after a prolonged period of depolarization at 0 mV, which inactivated IK(A) and IK(V), but not IK(N). When exposed to a hypoxic solution, the O2 tension near the cell fell from 125±6 to 14±2 mmHg (n=20), resulting in a slow depolarization of the myocyte membrane to −35±3 mV (n=16). The depolarization occurred without a change in the amplitude of IK(V) or IK(A), but it was accompanied by 60% inhibition of IK(N) at 0 mV. Our findings suggest that the resting potential of rabbit pulmonary artery myocytes depends on IK(N), and that inhibition of IK(N) may mediate the depolarization induced by hypoxia. British Journal of Pharmacology (1997) 120, 1461–1470; doi:10.1038/sj.bjp.0701075