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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2020
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.
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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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