| First Author | Chopra R | Year | 2018 |
| Journal | PLoS One | Volume | 13 |
| Issue | 5 | Pages | e0198040 |
| PubMed ID | 29847609 | Mgi Jnum | J:262838 |
| Mgi Id | MGI:6161514 | Doi | 10.1371/journal.pone.0198040 |
| Citation | Chopra R, et al. (2018) Dendritic potassium channel dysfunction may contribute to dendrite degeneration in spinocerebellar ataxia type 1. PLoS One 13(5):e0198040 |
| abstractText | 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 improves motor performance and mitigates dendritic degeneration in SCA1 mice. These results suggest that reduced expression of K+ channels results in persistently increased dendritic excitability at all stages of disease in SCA1, which in turn may contribute to the dendritic degeneration that precedes cell loss. |
