Shaw and Shal voltage‐gated potassium channels mediate circadian changes in Drosophila clock neuron excitability

Abstract

As in mammals, Drosophila circadian clock neurons display rhythms of activity with higher action potential firing rates and more positive resting membrane potentials during the day. This rhythmic excitability has been widely observed but, critically, its regulation remains unresolved. We have characterized and modelled the changes underlying these electrical activity rhythms in the lateral ventral clock neurons (LNvs). We show that currents mediated by the voltage‐gated potassium channels Shaw (Kv3) and Shal (Kv4) oscillate in a circadian manner. Disruption of these channels, by expression of dominant negative (DN) subunits, leads to changes in circadian locomotor activity and shortens lifespan. LNv whole‐cell recordings then show that changes in Shaw and Shal currents drive changes in action potential firing rate and that these rhythms are abolished when the circadian molecular clock is stopped. A whole‐cell biophysical model using Hodgkin‐Huxley equations can recapitulate these changes in electrical activity. Based on this model and by using dynamic clamp to manipulate clock neurons directly, we can rescue the pharmacological block of Shaw and Shal, restore the firing rhythm, and thus demonstrate the critical importance of Shaw and Shal. Together, these findings point to a key role for Shaw and Shal in controlling circadian firing of clock neurons and show that changes in clock neuron currents can account for this. Moreover, with dynamic clamp we can switch the LNvs between morning‐like and evening‐like states of electrical activity. We conclude that changes in Shaw and Shal underlie the daily oscillation in LNv firing rate.

The salmon louse genome: copepod features and parasitic adaptations

“…Furthermore, several copies of a gene with Blast hit to the protein Timeless [128], known for regulating circadian rhythm in Drosophila , are among the down regulated transcripts. Among the downregulated genes we also find three known for regulating circadian rhythm in Drosophila ; Shab, Shaw and Cycle [129, 130]. This may reflect the transformation from being a planktonic organism with diurnal migration [131] to a parasitic lifestyle.…”

High-Frequency Neuronal Bursting is Essential for Circadian and Sleep Behaviors inDrosophila

“…In Drosophila, several ion channels have already been found to play roles in different aspects of circadian function, such as the calcium dependent voltage-gated potassium channel slowpoke (slo; Ceriani et al, 2002;Fernandez et al, 2007) and its binding protein (slob; Ceriani et al, 2002;Jaramillo et al, 2004;Tabuchi et al, 2018), the cation channel narrow abdomen (na; Nash et al, 2002;Lear et al, 2005;Flourakis et al, 2015), the voltage-gated potassium channel Shaw (Hodge and Stanewsky, 2008;Buhl et al, 2016;Smith et al, 2019), the inward rectifying potassium channel Ir (Ruben et al, 2012), the temperature sensitive trpA1 channel (Lee and Montell, 2013), the potassium channel hyperkinetic (hk; Fogle et al, 2015) and the voltage-gated potassium channel Shal (Feng et al, 2018;Smith et al, 2019). Under the hypothesis that additional ion channels are involved in determining the characteristic physiological properties of the LNvs that ensure circadian organization of locomotor activity, we performed a behavioral genetic screen downregulating candidate ion channels using RNA interference (RNAi) specifically in LNvs.…”

The E3 ubiquitin ligase adaptor Tango10 links the core circadian clock to neuropeptide and behavioral rhythms

“…S11 A and C), providing further evidence for a The E3 ubiquitin ligase adaptor Tango10 links the core circadian clock to neuropeptide and behavioral rhythms reduction of the 4-AP-sensitive current in Tango10 lLNv. Interestingly, Shal gene expression and current levels are more elevated in the evening consistent with these 4-AP effects (48,50).…”