The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively Regulates Nociception
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+ cha...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718313743 |
| _version_ | 1818262901467643904 |
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| author | Kia C.E. Walcott Stephanie E. Mauthner Asako Tsubouchi Jessica Robertson W. Daniel Tracey |
| author_facet | Kia C.E. Walcott Stephanie E. Mauthner Asako Tsubouchi Jessica Robertson W. Daniel Tracey |
| author_sort | Kia C.E. Walcott |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-12T19:10:29Z |
| format | Article |
| id | doaj.art-9d9e80a0e21e45aca8db49b2f06915ac |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T19:10:29Z |
| publishDate | 2018-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9d9e80a0e21e45aca8db49b2f06915ac2022-12-22T00:14:51ZengElsevierCell Reports2211-12472018-09-01241231253132.e3The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively Regulates NociceptionKia C.E. Walcott0Stephanie E. Mauthner1Asako Tsubouchi2Jessica Robertson3W. Daniel Tracey4Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USAGill Center for Biomolecular Research, Indiana University, Bloomington, IN, USA; Department of Biology, Indiana University, Bloomington, IN, USADepartment of Anesthesiology, Duke University Medical Center, Durham, NC, USADepartment of Cell Biology, Duke University Medical Center, Durham, NC, USAGill Center for Biomolecular Research, Indiana University, Bloomington, IN, USA; Department of Biology, Indiana University, Bloomington, IN, USA; Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC, USA; Corresponding authorSummary: 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 screenhttp://www.sciencedirect.com/science/article/pii/S2211124718313743 |
| spellingShingle | Kia C.E. Walcott Stephanie E. Mauthner Asako Tsubouchi Jessica Robertson W. Daniel Tracey The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively Regulates Nociception Cell Reports |
| title | The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively Regulates Nociception |
| title_full | The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively Regulates Nociception |
| title_fullStr | The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively Regulates Nociception |
| title_full_unstemmed | The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively Regulates Nociception |
| title_short | The Drosophila Small Conductance Calcium-Activated Potassium Channel Negatively Regulates Nociception |
| title_sort | drosophila small conductance calcium activated potassium channel negatively regulates nociception |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718313743 |
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