Dendritic potassium channel dysfunction may contribute to dendrite degeneration in spinocerebellar ataxia type 1

PloS One
Ravi ChopraVikram G Shakkottai

Abstract

Purkinje neuron dendritic degeneration precedes cell loss in cerebellar ataxia, but the basis for dendritic vulnerability in ataxia remains poorly understood. Recent work has suggested that potassium (K+) channel dysfunction and consequent spiking abnormalities contribute to Purkinje neuron degeneration, but little attention has been paid to how K+ channel dysfunction impacts dendritic excitability and the role this may play in the degenerative process. We examined the relationship between K+ channel dysfunction, dendritic excitability and dendritic degeneration in spinocerebellar ataxia type 1 (SCA1). Examination of published RNA sequencing data from SCA1 mice revealed reduced expression of several K+ channels that are important regulators of excitability in Purkinje neuron dendrites. Patch clamp recordings in Purkinje neurons from SCA1 mice identified increased dendritic excitability in the form of enhanced back-propagation of action potentials and an increased propensity to produce dendritic calcium spikes. Dendritic excitability could be rescued by restoring expression of large-conductance calcium-activated potassium (BK) channels and activating other K+ channels with baclofen. Importantly, this treatment combination improv...Continue Reading

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Apr 20, 2020·Cellular and Molecular Life Sciences : CMLS·Leon Tejwani, Janghoo Lim
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Datasets Mentioned

BETA
GSE75778

Software Mentioned

Systat
Excel
pClamp
10
NIS Elements
GraphPad Prism
cellSens Standard
SigmaPlot

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