We are interested in determining the role of specific voltage-gated (Kv) potassium channels (and the different subunit proteins that comprise them) in neuronal excitability. Kv1.1 channel subunits are densely localised in the axon terminals of cerebellar basket cells, which impinge on cerebellar Purkinje cells. In this study we investigated the role of Kv1.1 subunits electrophysiologically using Kv1.1 null mutant mice (Smart et al. 1998), and selective potassium channel toxins. Whole-cell patch-clamp recordings of spontaneous inhibitory postsynaptic currents (sIPSCs) were obtained from Purkinje cells in parasagittal cerebellar slices from Kv1.1 null mice (postnatal day 25). Wild-type littermates of the same age were used as controls, and experiments were performed blind. Mice were bred and humanely killed under UK Home Office licence, in accordance with UK legislation.

Both amplitude and frequency of sIPSCs were significantly greater in Kv1.1 null mutant mice (n = 16), compared with wild-type littermates (n = 12, P < 0.05, Student’s unpaired t test). In the presence of δ-dendrotoxin (δ-DTX, 100 nM), a selective Kv1.1 subunit blocker, the amplitude and frequency of sIPSCs was increased significantly in wild-type mice (P < 0.05). The changes in sIPSC amplitude and frequency were quantified as an activity index (the activity index is the product of the toxin/control amplitude ratio and the toxin/control frequency ratio; see Southan & Robertson, 1998). The activity index for δ-DTX in wild-type mice was 2.1 ± 0.2 (n = 12, mean ± S.E.M.). In Kv1.1 null mutant mice, the application of δ-DTX (100 nM) had no effect on sIPSC amplitude and frequency (activity index 1.0 ± 0.1, n = 6, P < 0.01 compared with wild-type). α-DTX, a Kv1.1 and 1.2 subunit blocker (100 nM), was applied following the addition of δ-DTX in all experiments. In wild-type mice, α-DTX further increased the amplitude and frequency of sIPSCs above that observed in δ-DTX (n = 10, activity index 1.9 ± 0.3). In Kv1.1 null mutants, α-DTX caused an increase in the amplitude and frequency of sIPSCs, similar to that observed in wild-type mice (n = 4, activity index 2.1 ± 0.3).

The Kv1.1 subunit is therefore not essential for synaptic transmission at this key cerebellar synapse, but its absence in the null mutant appears to increase the overall inhibitory tone. Future studies are planned with the other components of Kv1 subunit channels present at this synapse.

This work was supported by The Wellcome Trust.

All procedures accord with current UK legislation.