Members of the twin-pore domain potassium (K⁺) channel family provide a molecular correlate for some neuronal ‘leak’ K⁺ conductances. Recently mRNAs for two members of this family, the pH-sensitive TASK-1 and TASK-3 channels, have been demonstrated in rat facial motoneurones (FMs) (Rajan et al. 2000; Talley et al. 2000). We have used whole-cell patch-clamp recordings and neonatal rat brainstem slices, prepared from humanely killed rats, to investigate whether these channels underlie the ‘leak’ K⁺ conductance inhibited by noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in FMs (Larkman & Kelly, 1992, 1998).

Results were obtained from 25 different FMs voltage clamped at -60 mV in the presence of ZD 7288 (5 µM) to block the hyperpolarisation-activated current, I_h. The pH sensitivity of FM input conductance was determined by superfusing the slice with external solution titrated to a range of different pH. Lowering the external pH from 7.3 to 6 evoked an inward current of -63 ± 7 pA (n = 9, mean ± S.E.M.) associated with a conductance decrease. Raising the external pH to 8 evoked an outward current of +48 ± 5 pA (n = 3) and a conductance increase. Both inward and outward pH-sensitive currents (I_pH) had linear current-voltage (I-V) relationships and reversed close to the predicted K⁺ equilibrium potential (E_K) (-93 ± 2 mV and -94 ± 4 mV for inward and outward I_pH, respectively). Averaged input conductance measurements (n = 10) at different external pH, expressed as a percentage of conductance at pH 7, could be described by a logistic function with a pK of 7.1 and a Hill coefficient of 1.4. The NA-sensitive current (I_NA) is also linear and reverses at the E_K (Larkman & Kelly, 1992). When external pH was lowered to 6.5, bath application of NA (10 µM) evoked an inward current of -34 ± 9 pA (n = 5). After increasing external pH to 7.7, NA evoked an inward current of -109 ± 19 pA in the same FMs (n = 5). External Ba²⁺ (200 µM to 2 mM) blocked both I_NA (n = 4) and I_pH (n = 3) at potentials negative to the reversal potential but were much less effective at potentials positive to the reversal level. External TEA chloride (30 mM) had no effect on I_NA or I_pH, but the addition of 4-AP (4 mM) blocked both I_NA and I_pH (n = 3). Zn²⁺ (100-500 µM) had no effect on I_NA or I_pH (n = 3).

In conclusion these biophysical and pharmacological data suggest a TASK-like channel mediates the ‘leak’ K⁺ conductance and that inhibition of this conductance underlies NA-evoked depolarisation of rat FMs.

This work was supported by the EU. E.M.P. holds a MRC studentship.