Function of the Shaw potassium channel within the Drosophila circadian clock

Abstract

Background: In addition to the molecular feedback loops, electrical activity has been shown to be important for the function of networks of clock neurons in generating rhythmic behavior. Most studies have used over-expression of foreign channels or pharmacological manipulations that alter membrane excitability. In order to determine the cellular mechanisms that regulate resting membrane potential (RMP) in the native clock of Drosophila we modulated the function of Shaw, a widely expressed neuronal pottasium (K+) channel known to regulate RMP in Drosophila central neurons. Methodology/Principle Findings: We show that Shaw is endogenously in clock neurons. Differential use of clock gene promoters was employed to express a range of transgene that either increase or decrease Shaw function in different clusters of clock neurons. Under LD conditions, increasing Shaw levels in all clock neurons (LNv, LNd, DN1, DN2 and DN3), or in subsets of clock (LNd and DNs or DNs alone) increases locomotor activity at night. In free-running conditions these manipulations result in arrhythmic locomotor activity without disruption of the molecular clock. Reducing Shaw in the DNA alone caused a dramatic lengthening of the behavioral period. Changing Shaw levels in all clock neurons also disrupts the rhythmic accumulation and levels of Pigment Dipersing Factor (PDF) in the dorsal projections of LNv neurons. However, changing Shaw levels solely in LNv neurons had little effect on locomotor activity or rhythmic accumulation of PDF. Conclusions/Significance: Based on our results it is likely that Shaw modulates pacemaker and output neuronal electrical activity that controls neurons in Shaw-mediated control of circadian behaviour. In conclusion, we have demonstrated a central role of Shaw for coordinated and rhythmic output from clock neurons. © 2008 Hodge, Stanewsky.