BackgroundRhythmic behaviors, such as walking and breathing, involve the coordinated activity of central pattern generators in the CNS, sensory feedback from the PNS, to motoneuron output to muscles. Unraveling the intrinsic electrical properties of these cellular components is essential to understanding this coordinated activity. Here, we examine the significance of the transient A-type K+ current (IA), encoded by the highly conserved Shal/Kv4 gene, in neuronal firing patterns and repetitive behaviors. While IA is present in nearly all neurons across species, elimination of IA has been complicated in mammals because of multiple genes underlying IA, and/or electrical remodeling that occurs in response to affecting one gene.Methodology/Principal FindingsIn Drosophila, the single Shal/Kv4 gene encodes the predominant IA current in many neuronal cell bodies. Using a transgenically expressed dominant-negative subunit (DNKv4), we show that IA is completely eliminated from cell bodies, with no effect on other currents. Most notably, DNKv4 neurons display multiple defects during prolonged stimuli. DNKv4 neurons display shortened latency to firing, a lower threshold for repetitive firing, and a progressive decrement in AP amplitude to an adapted state. We record from identified motoneurons and show that Shal/Kv4 channels are similarly required for maintaining excitability during repetitive firing. We then examine larval crawling, and adult climbing and grooming, all behaviors that rely on repetitive firing. We show that all are defective in the absence of Shal/Kv4 function. Further, knock-out of Shal/Kv4 function specifically in motoneurons significantly affects the locomotion behaviors tested.Conclusions/SignificanceBased on our results, Shal/Kv4 channels regulate the initiation of firing, enable neurons to continuously fire throughout a prolonged stimulus, and also influence firing frequency. This study shows that Shal/Kv4 channels play a key role in repetitively firing neurons during prolonged input/output, and suggests that their function and regulation are important for rhythmic behaviors.

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