Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons
Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na+-dependent K+ (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/10013 |
| _version_ | 1811236868219469824 |
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| author | Pedro L Martinez-Espinosa Jianping Wu Chengtao Yang Vivian Gonzalez-Perez Huifang Zhou Hongwu Liang Xiao-Ming Xia Christopher J Lingle |
| author_facet | Pedro L Martinez-Espinosa Jianping Wu Chengtao Yang Vivian Gonzalez-Perez Huifang Zhou Hongwu Liang Xiao-Ming Xia Christopher J Lingle |
| author_sort | Pedro L Martinez-Espinosa |
| collection | DOAJ |
| description | Two mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na+-dependent K+ (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations. |
| first_indexed | 2024-04-12T12:15:29Z |
| format | Article |
| id | doaj.art-3e7131681543466e9bccd504328f46df |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:15:29Z |
| publishDate | 2015-11-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-3e7131681543466e9bccd504328f46df2022-12-22T03:33:26ZengeLife Sciences Publications LtdeLife2050-084X2015-11-01410.7554/eLife.10013Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neuronsPedro L Martinez-Espinosa0Jianping Wu1Chengtao Yang2Vivian Gonzalez-Perez3Huifang Zhou4Hongwu Liang5Xiao-Ming Xia6Christopher J Lingle7Department of Anesthesiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, United StatesDepartment of Anesthesiology, Washington University School of Medicine, St. Louis, United StatesTwo mammalian genes, Kcnt1 and Kcnt2, encode pore-forming subunits of Na+-dependent K+ (KNa) channels. Progress in understanding KNa channels has been hampered by the absence of specific tools and methods for rigorous KNa identification in native cells. Here, we report the genetic disruption of both Kcnt1 and Kcnt2, confirm the loss of Slo2.2 and Slo2.1 protein, respectively, in KO animals, and define tissues enriched in Slo2 expression. Noting the prevalence of Slo2.2 in dorsal root ganglion, we find that KO of Slo2.2, but not Slo2.1, results in enhanced itch and pain responses. In dissociated small diameter DRG neurons, KO of Slo2.2, but not Slo2.1, abolishes KNa current. Utilizing isolectin B4+ neurons, the absence of KNa current results in an increase in action potential (AP) firing and a decrease in AP threshold. Activation of KNa acts as a brake to initiation of the first depolarization-elicited AP with no discernible effect on afterhyperpolarizations.https://elifesciences.org/articles/10013itchSLO2KNa currentDRGpain |
| spellingShingle | Pedro L Martinez-Espinosa Jianping Wu Chengtao Yang Vivian Gonzalez-Perez Huifang Zhou Hongwu Liang Xiao-Ming Xia Christopher J Lingle Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons eLife itch SLO2 KNa current DRG pain |
| title | Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons |
| title_full | Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons |
| title_fullStr | Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons |
| title_full_unstemmed | Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons |
| title_short | Knockout of Slo2.2 enhances itch, abolishes KNa current, and increases action potential firing frequency in DRG neurons |
| title_sort | knockout of slo2 2 enhances itch abolishes kna current and increases action potential firing frequency in drg neurons |
| topic | itch SLO2 KNa current DRG pain |
| url | https://elifesciences.org/articles/10013 |
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