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 Ca 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.

SummaryInhibition 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, resulted in marked hypersensitive nociception behaviors.In more detailed studies of SK, we found that hypersensitive phenotypes could be recapitulated with a genetically null allele. Importantly, the null mutant phenotype could be rescued with tissue specific expression of an SK cDNA in nociceptors. Optical recordings from nociceptive neurons showed a significant increase in mechanically activated Ca 2+ signals in SK mutant nociceptors. SK showed expression in peripheral neurons. Interestingly SK proteins localized to axons of these neurons but were not detected in dendrites. Our findings suggest a major role for SK channels in the regulation of nociceptor excitation and they are inconsistent with the hypothesis that the important site of action is within dendrites.