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bioRxiv · 10.1101/208868

The Drosophila SK potassium channel negatively regulates nociception.

Walcott, K.·Mauthner, S.·Tsubouchi, A.·Robertson, J.·Tracey, D.
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Abstract

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, 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 Ca2+ 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.\n\nHighlights-Specific potassium channels regulate nociceptor excitability.\n-SK channels have a critical function in nociception.\n-SK channels specifically localize to sensory axons\n-SK channels are not detectable in sensory dendrites.

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Walcott, K., Mauthner, S., Tsubouchi, A., Robertson, J., Tracey, D.. 2017-10-26. The Drosophila SK potassium channel negatively regulates nociception.. https://doi.org/10.1101/208868

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