The resting potential of pulmonary artery myocytes depends upon a non-inactivating K⁺ conductance (I_KN) with low sensitivity to block by 4-aminopyridine and quinine and insensitivity to tetraethylammonium ions (Evans et al. 1996). Both acute (Osipenko et al. 1997) and chronic (Osipenko et al. 1998) hypoxia inhibit I_KN and cause depolarisation. The two-pore domain K channel, TASK-1 (KCNK3), has similar pharmacology and contributes to the resting potential in neuronal cells. It has been implicated in the hypoxia-induced depolarisation of cerebellar granule neurons (Plant et al. 2002) and carotid body cells (Buckler et al. 2000).

We investigated the potential role of TASK-1 channels in mediating I_KN and the resting potential in pulmonary artery myocytes, isolated from rabbits humanely killed with pentobarbitone (80 mg kg^-1, I.V.). The resting membrane potential and amplitude of I_KN at a holding potential of 0 mV were measured in rabbit pulmonary artery smooth muscle cells, using the whole-cell patch-clamp technique. Drugs were applied in the extracellular solution. The composition of the pipette solution was varied to alter the intracellular concentrations of Ca²⁺ or ATP.

Reducing extracellular pH from 7.3 to 6.3 reduced the amplitude of I_KN by ~70 %, while increasing pH to 8.3 increased current amplitude by ~10 %. These effects were accompanied by changes in membrane potential from around -45 mV (pH7.3) to -25 mV (pH 6.3) or -50 mV (pH 8.3). Halothane (1-2 mM) had a variable effect, but usually produced a transient increase in current amplitude (of 32 ± 16 %, n = 8; mean ± S.E.M.) lasting ~30 s, followed by a 43 ± 10 % decrease in amplitude. It had a biphasic effect on membrane potential, brief hyperpolarisation being followed by depolarisation. At 100 µM, Zn²⁺ inhibited I_KN by 56 ± 10 % (n = 4) and almost abolished the resting potential. Removing extracellular Ca²⁺, applying the Ca²⁺ ionophore A23187 (10 µM), or varying the intracellular EGTA concentration (0.05-5 mM) had no significant effect on I_KN amplitude. Varying the intracellular ATP concentration (0-5 mM) also failed to affect I_KN.

These results are consistent with a major role for TASK-1 channels in mediating the resting K⁺ conductance and membrane potential of pulmonary artery smooth muscle cells.

This work was supported by the British Heart Foundation and BBSRC.