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bioRxiv · 10.1101/2020.02.20.957571

A knock-in Drosophila model supports a conserved link between potassium channelopathy and involuntary movement

Kratschmer, P.·Buhl, E.·Chen, K.-F.·Lowe, S.·Kullmann, D. M.·Hodge, J. J. L.·Jepson, J. E. C.
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Abstract

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.

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Kratschmer, P., Buhl, E., Chen, K.-F., Lowe, S., Kullmann, D. M., Hodge, J. J. L., Jepson, J. E. C.. 2020-02-20. A knock-in Drosophila model supports a conserved link between potassium channelopathy and involuntary movement. https://doi.org/10.1101/2020.02.20.957571

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