Specific alteration of spontaneous GABAergic inhibition in cerebellar Purkinje cells in mice lacking the potassium channel Kv1.1

In the cerebellum, the basket cell innervation on Purkinje cells provides a major GABAergic inhibitory control of the single efferent output from the cerebellum. The Shaker-type K channel Kv1.1 is localized at the axon arbori zation preceding the terminal of the basket cells and is therefore a potent ial candidate for regulating the GABAergic inhibition. In this study, we di rectly assess this role of Kv1.1 by electrophysiological analysis of Kv1.1 null mutant mice. Whole-cell patch-clamp recordings of spontaneous IPSCs (s IPSCs) were made from Purkinje cells in thin cerebellar slices from postnat al day (P)10-15 Kv1.1-null mutants using wild-type littermates as controls. The null mutation confers a very specific change in the sIPSC: the frequen cy increases about twofold, without accompanying changes in the mean and va riance of its amplitude distribution. The frequency and amplitude of the mi niature IPSCs (mIPSCs) are unaffected. Spontaneous firing rate of the baske t cells is unaltered. Evoked IPSC does not show multiple activity in the mu tants. Motor skills tests show that Kv1.1 null mice display a compromised a bility to maintain balance on a thin stationary rod. We conclude that the K v1.1 null mutation results in a persistent elevation of the tonic inhibitor y tone on the cerebellum Purkinje cell efferent and that this is not fully compensated for by residual Shaker-type channels. We further suggest that t he increase in inhibitory tone in the mutants might underlie the behavioral deficits. At the cellular level, we propose that Kv1.1 deletion enhances e xcitability of the basket cells by selectively enhancing the likelihood of action potential propagation past axonal branch points.