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Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity

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Abstract

Purkinje neurons, the sole output of the cerebellar cortex, deliver GABA-mediated inhibition to the deep cerebellar nuclei. To subserve this critical function, Purkinje neurons fire repetitively, and at high frequencies, features that have been linked to the unique properties of the voltage-gated sodium (Nav) channels expressed. In addition to the rapidly activating and inactivating, or transient, component of the Nav current (INaT) present in many types of central and peripheral neurons, Purkinje neurons, also expresses persistent (INaP) and resurgent (INaR) Nav currents. Considerable progress has been made in detailing the biophysical properties and identifying the molecular determinants of these discrete Nav current components, as well as defining their roles in the regulation of Purkinje neuron excitability. Here, we review this important work and highlight the remaining questions about the molecular mechanisms controlling the expression and the functioning of Nav currents in Purkinje neurons. We also discuss the impact of the dynamic regulation of Nav currents on the functioning of individual Purkinje neurons and cerebellar circuits.

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Acknowledgements

The authors thank Richard Wilson for technical assistance in creating figures. Financial support provided by the National Institutes of Health (R01NS065761 to J.M.N., F32NS090765 to J.L.R.) is also gratefully acknowledged.

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  1. Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Joseph L. Ransdell & Jeanne M. Nerbonne

  2. Department of Medicine, Washington University School of Medicine, Box 8086, 660 South Euclid Avenue, St. Louis, MO, 63110, USA

    Joseph L. Ransdell & Jeanne M. Nerbonne

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Ransdell, J.L., Nerbonne, J.M. Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity. Cell. Mol. Life Sci. 75, 3495–3505 (2018). https://doi.org/10.1007/s00018-018-2868-y

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