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Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K(V)6.4 Subunit
By studying healthy women who do not request analgesia during their first delivery, we investigate genetic effects on labor pain. Such women have normal sensory and psychometric test results, except for significantly higher cuff pressure pain. We find an excess of heterozygotes carrying the rare all...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383234/ https://www.ncbi.nlm.nih.gov/pubmed/32697988 http://dx.doi.org/10.1016/j.celrep.2020.107941 |
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author | Lee, Michael C. Nahorski, Michael S. Hockley, James R.F. Lu, Van B. Ison, Gillian Pattison, Luke A. Callejo, Gerard Stouffer, Kaitlin Fletcher, Emily Brown, Christopher Drissi, Ichrak Wheeler, Daniel Ernfors, Patrik Menon, David Reimann, Frank Smith, Ewan St. John Woods, C. Geoffrey |
author_facet | Lee, Michael C. Nahorski, Michael S. Hockley, James R.F. Lu, Van B. Ison, Gillian Pattison, Luke A. Callejo, Gerard Stouffer, Kaitlin Fletcher, Emily Brown, Christopher Drissi, Ichrak Wheeler, Daniel Ernfors, Patrik Menon, David Reimann, Frank Smith, Ewan St. John Woods, C. Geoffrey |
author_sort | Lee, Michael C. |
collection | PubMed |
description | By studying healthy women who do not request analgesia during their first delivery, we investigate genetic effects on labor pain. Such women have normal sensory and psychometric test results, except for significantly higher cuff pressure pain. We find an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4. The rare variant K(V)6.4-Met419 has a dominant-negative effect and cannot modulate the voltage dependence of K(V)2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, Kcng4 (K(V)6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express K(V)2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a. In neurons overexpressing K(V)6.4-Met419, the voltage dependence of inactivation for K(V)2.1 is more depolarized compared with neurons overexpressing K(V)6.4. Finally, K(V)6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that K(V)6.4 can influence human labor pain by modulating the excitability of uterine nociceptors. |
format | Online Article Text |
id | pubmed-7383234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-73832342020-07-30 Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K(V)6.4 Subunit Lee, Michael C. Nahorski, Michael S. Hockley, James R.F. Lu, Van B. Ison, Gillian Pattison, Luke A. Callejo, Gerard Stouffer, Kaitlin Fletcher, Emily Brown, Christopher Drissi, Ichrak Wheeler, Daniel Ernfors, Patrik Menon, David Reimann, Frank Smith, Ewan St. John Woods, C. Geoffrey Cell Rep Article By studying healthy women who do not request analgesia during their first delivery, we investigate genetic effects on labor pain. Such women have normal sensory and psychometric test results, except for significantly higher cuff pressure pain. We find an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4. The rare variant K(V)6.4-Met419 has a dominant-negative effect and cannot modulate the voltage dependence of K(V)2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, Kcng4 (K(V)6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express K(V)2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a. In neurons overexpressing K(V)6.4-Met419, the voltage dependence of inactivation for K(V)2.1 is more depolarized compared with neurons overexpressing K(V)6.4. Finally, K(V)6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that K(V)6.4 can influence human labor pain by modulating the excitability of uterine nociceptors. Cell Press 2020-07-21 /pmc/articles/PMC7383234/ /pubmed/32697988 http://dx.doi.org/10.1016/j.celrep.2020.107941 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Michael C. Nahorski, Michael S. Hockley, James R.F. Lu, Van B. Ison, Gillian Pattison, Luke A. Callejo, Gerard Stouffer, Kaitlin Fletcher, Emily Brown, Christopher Drissi, Ichrak Wheeler, Daniel Ernfors, Patrik Menon, David Reimann, Frank Smith, Ewan St. John Woods, C. Geoffrey Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K(V)6.4 Subunit |
title | Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K(V)6.4 Subunit |
title_full | Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K(V)6.4 Subunit |
title_fullStr | Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K(V)6.4 Subunit |
title_full_unstemmed | Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K(V)6.4 Subunit |
title_short | Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K(V)6.4 Subunit |
title_sort | human labor pain is influenced by the voltage-gated potassium channel k(v)6.4 subunit |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383234/ https://www.ncbi.nlm.nih.gov/pubmed/32697988 http://dx.doi.org/10.1016/j.celrep.2020.107941 |
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