title: Specific alteration of spontaneous GABAergic inhibition in cerebellar purkinje cells in mice lacking the potassium channel Kv1. 1.
abstract: 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 arborization preceding the terminal of the basket cells and is therefore a potential candidate for regulating the GABAergic inhibition. In this study, we directly assess this role of Kv1.1 by electrophysiological analysis of Kv1.1 null mutant mice. Whole-cell patch-clamp recordings of spontaneous IPSCs (sIPSCs) were made from Purkinje cells in thin cerebellar slices from postnatal 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 frequency increases about twofold, without accompanying changes in the mean and variance of its amplitude distribution. The frequency and amplitude of the miniature IPSCs (mIPSCs) are unaffected. Spontaneous firing rate of the basket cells is unaltered. Evoked IPSC does not show multiple activity in the mutants. Motor skills tests show that Kv1.1 null mice display a compromised ability to maintain balance on a thin stationary rod. We conclude that the Kv1.1 null mutation results in a persistent elevation of the tonic inhibitory tone on the cerebellum Purkinje cell efferent and that this is not fully compensated for by residual Shaker-type channels. We further suggest that the increase in inhibitory tone in the mutants might underlie the behavioral deficits. At the cellular level, we propose that Kv1.1 deletion enhances excitability of the basket cells by selectively enhancing the likelihood of action potential propagation past axonal branch points.
authors: Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706, USA.
authors: C L
authors: CL
authors: Zhang
authors: A
authors: A
authors: Messing
authors: S Y
authors: SY
authors: Chiu
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D051662:Kv1.1 Potassium Channel; D051379:Mice; D008817:Mice, Mutant Strains; D009048:Motor Skills / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000032:analysis*; D024642:Potassium Channels, Voltage-Gated; D011689:Purkinje Cells / Q000737:chemistry / Q000187:drug effects*
chemical_list: D018756:GABA Antagonists; C496947:Kcna1 protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel