The ability of animals to detect sensory stimulation, generate appropriate motor responses, and adapt detection mechanisms to changes in stimuli is crucial for survival. All of this signaling depends on the coordinated action of ion channels in the membranes of neurons. For example, there are Na+ channels specially evolved to carry out the fast depolarization of the neuronal membrane, as well as a wide range of K+ channels that subsequently repolarize the membrane and shape the action potential (AP) output of a neuron. In the proposed studies, the PI will test the role of KNa/slo2 channels, whose molecular identity has, relatively speaking, only recently been described. KNa/slo2 channels are Na+-activated K+ channels, which may have evolved to provide a protective ?brake? on membrane depolarization when neurons are over-stimulated. Although a neuroprotective role against over-excitation and a physiological role in sensory transduction/adaptation have been suggested, these role(s) of KNa/slo2 channels remain controversial. The PI proposes to use Drosophila as an in vivo model to address questions about how Na+ activates KNa/slo2 channels to affect neuronal signaling and behavior. The studies will look directly at AP firing and neuronal excitability, and explore behavioral effects on responsiveness to touch stimulation. Finally, the studies will use hyper-excitable genetic mutants with enhanced Na+ currents to test whether KNa/dslo2 channels are indeed able to counter over-excitation. 1
In the proposed studies, the PI will test the role of KNa/slo2 channels, whose molecular identity has, relatively speaking, only recently been described. KNa/slo2 channels are Na+-activated K+ channels, which may have evolved to provide a protective ?brake? on membrane depolarization when neurons are over- stimulated. Although a neuroprotective role against over-excitation and a physiological role in sensory transduction/adaptation have been suggested, these role(s) of KNa/slo2 channels remain controversial. The PI proposes to use Drosophila as an in vivo model to investigate KNa/slo2 channels, and their Na+ sensitivity, in these potential roles. The studies will look directly at neuronal signaling and behavioral roles in the responsiveness to touch stimulation. Finally, the studies will use hyper-excitable genetic mutants, with seizure-like behavior, to test whether KNa/dslo2 channels are indeed able to counter over-excitation. If KNa/slo2 channels can indeed act as a neuroprotective mechanism for hyper-excitation, they may also provide a valuable therapeutic target for controlling hyperactivity in pathological conditions. 1
