REGULATION OF THE RESTING POTENTIAL OF RABBIT PULMONARY-ARTERY MYOCYTES BY A LOW-THRESHOLD, O-2-SENSING POTASSIUM CURRENT

1 The contributions of specific K+ currents to the resting membrane po tential of rabbit isolated, pulmonary artery myocytes, and their modul ation by hypoxia, were investigated by use of the whole-cell, patch-cl amp technique. 2 In the presence of 10 mu M glibenclamide the resting potential (-50 +/- 4 mV, n = 18) was unaffected by 10 mu M tetraethyla mmonium ions, 200 nM charybdotoxin, 200 nM iberiotoxin, 100 mu M ouaba in or 100 mu M digitoxin. The negative potential was therefore maintai ned without ATP-sensitive (K-ATP) or large conductance Ca2+-sensitive (BKCa) K channels, and without the Na+-K(+)ATPase. 3 The resting poten tial, the delayed rectifier current (I-K(V)) and the A-like K+ current (I-K(A)) were all reduced in a concentration-dependent manner by 4-am inopyridine (4-AP) and by quinine. 4 4-AP was equally potent at reduci ng the resting potential and I-K(V), 10 mM causing depolarization from -44 mV to -22 mV with accompanying inhibition of I-K(V) by 56% and I- K(A) by 79%. In marked contrast, the effects of quinine on resting pot ential were poorly correlated with its effects on both IK(A) and I-K(V ). At 10 mM, quinine reduced I-K(V) and I-K(V) by 47% and 38%, respect ively, with no change in the resting potential. At 100 mu M, both curr ents were almost abolished while the resting potential was reduced <50 %. Raising the concentration to 1 mM had little further effect on I-K( A) or I-K(V), but essentially abolished the resting potential. 5 Reduc tion of the resting potential by quinine was correlated with inhibitio n of a voltage-gated, low threshold, non-inactivating K+ current, I-K( N) Thus, 100 mu M quinine reduced both I-K(N) and the resting potentia l by around 50%. 6 The resting membrane potential was the same whether measured after clamping the cell at -80 mV, or immediately after a pr olonged period of depolarization at 0 mV, which inactivated I-K(A) and I-K(V), but not I-K(N). 7 When exposed to a hypoxic solution, the O-2 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 amp litude of I-K(V) or I-K(A), but it was accompanied by 60% inhibition o f I-K(N) at 0 mV. 8 Our findings suggest that the resting potential of rabbit pulmonary artery myocytes depends on I-K(N) and that inhibitio n of I-K(N) may mediate the depolarization induced by hypoxia.