Rescue of Motor Coordination by Purkinje Cell-Targeted Restoration of Kv3.3 Channels inKcnc3-Null Mice RequiresKcnc1
Open Access
- 16 December 2009
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 29 (50), 15735-15744
- https://doi.org/10.1523/jneurosci.4048-09.2009
Abstract
The role of cerebellar Kv3.1 and Kv3.3 channels in motor coordination was examined with an emphasis on the deep cerebellar nuclei (DCN). Kv3 channel subunits encoded byKcncgenes are distinguished by rapid activation and deactivation kinetics that support high-frequency, narrow action potential firing. Previously we reported that increased lateral deviation while ambulating and slips while traversing a narrow beam of ataxicKcnc3-null mice were corrected by restoration of Kv3.3 channels specifically to Purkinje cells, whereasKcnc3-mutant mice additionally lacking oneKcnc1allele were partially rescued. Here, we report mice lacking allKcnc1andKcnc3alleles exhibit no such rescue. For Purkinje cell output to reach the rest of the brain it must be conveyed by neurons of the DCN or vestibular nuclei. AsKcnc1, but notKcnc3, alleles are lost, mutant mice exhibit increasing gait ataxia accompanied by spike broadening and deceleration in DCN neurons, suggesting the facet of coordination rescued by Purkinje-cell-restricted Kv3.3 restoration in mice lacking justKcnc3is hypermetria, while gait ataxia emerges when additionallyKcnc1alleles are lost. Thus, fast repolarization in Purkinje cells appears important for normal movement velocity, whereas DCN neurons are a prime candidate locus where fast repolarization is necessary for normal gait patterning.Keywords
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