A knock-in Drosophila model supports a conserved link between potassium channelopathy and involuntary movement
| Autor: | Simon Lowe, James E.C. Jepson, Edgar Buhl, Patrick Kratschmer, James J L Hodge, Dimitri M. Kullmann, Ko-Fan Chen |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
BK channel biology Motor control Afterhyperpolarization Paroxysmal dyskinesia medicine.disease 03 medical and health sciences Electrophysiology 0302 clinical medicine Channelopathy Gene knockin Mutation (genetic algorithm) biology.protein medicine Neuroscience 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/2020.02.20.957571 |
| Popis: | BackgroundGenetic and in vitro studies have linked a heterozygous gain-of-function mutation (D434G) in the hSlo1 BK (Big potassium) channel to paroxysmal dyskinesia. However, support for this linkage from in vivo models has been lacking.ObjectivesWe aimed to re-create the equivalent mutation to hSlo1 D434G in the fruit fly, Drosophila, and examine how this mutation altered movement and action potential waveforms.MethodsWe generated a knock-in Drosophila model of hSlo1 D434G. We used video-tracking and infra-red beam-break systems to test whether locomotion was altered in this model, and patch-clamp electrophysiology to determine how the mutation affected action potential waveforms.ResultsWe identified profound motor dysfunction and sporadic leg twitches, as well as a reduced width and an enhancement of the afterhyperpolarization phase of action potentials, in the model background.ConclusionOur results support a conserved relationship between enhanced BK channel function and disrupted motor control across distantly related species. |
| Databáze: | OpenAIRE |
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