| Summary: | Summary: Inhibition of nociceptor activity is important for the prevention of spontaneous pain and hyperalgesia. To identify the critical K+ channels that regulate nociceptor excitability, we performed a forward genetic screen using a Drosophila larval nociception paradigm. Knockdown of three K+ channel loci, the small conductance calcium-activated potassium channel (SK), seizure, and tiwaz, causes marked hypersensitive nociception behaviors. In more detailed studies of SK, we found that hypersensitive phenotypes can be recapitulated with a genetically null allele. Optical recordings from nociceptive neurons showed a significant increase in mechanically activated Ca2+ signals in SK mutant nociceptors. SK is expressed in peripheral neurons, including nociceptive neurons. Interestingly, SK proteins localize to axons of these neurons but are not detected in dendrites. Our findings suggest a major role for SK channels in the regulation of nociceptor excitation and are inconsistent with the hypothesis that the important site of action is within dendrites. : Walcott et al. performed a forward genetic screen and identify three potassium channel subunits that negatively regulate nociception in Drosophila larvae. In a more detailed investigation of the SK channel, null mutants, rescue experiments, optical recordings, and protein localization studies indicate a functional role for SK in nociceptor excitability. Keywords: nociception, pain, potassium channel, small conductance calcium-activated potassium channel, Kv channel, behavior, physiology, calcium imaging, genetic screen
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