1. Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K V 6.4 Subunit.
- Author
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Lee MC, Nahorski MS, Hockley JRF, Lu VB, Ison G, Pattison LA, Callejo G, Stouffer K, Fletcher E, Brown C, Drissi I, Wheeler D, Ernfors P, Menon D, Reimann F, Smith ESJ, and Woods CG
- Subjects
- Adult, Alleles, Amino Acid Sequence, Analgesics pharmacology, Animals, Base Sequence, Cell Membrane metabolism, Cognition, Cohort Studies, Emotions, Female, Ganglia, Spinal metabolism, Heterozygote, Humans, Ion Channel Gating genetics, Labor Pain genetics, Labor Pain physiopathology, Male, Mice, Inbred C57BL, Models, Biological, Mutation genetics, Nociceptors metabolism, Pain Threshold, Polymorphism, Single Nucleotide genetics, Potassium Channels, Voltage-Gated chemistry, Potassium Channels, Voltage-Gated genetics, Pregnancy, Protein Multimerization, Sensory Receptor Cells metabolism, Shab Potassium Channels metabolism, Subcellular Fractions metabolism, Uterus innervation, Labor Pain metabolism, Potassium Channels, Voltage-Gated metabolism, Protein Subunits metabolism
- Abstract
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 KV 2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, Kcng4 (KV 6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express KV 2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a. In neurons overexpressing KV 6.4-Met419, the voltage dependence of inactivation for KV 2.1 is more depolarized compared with neurons overexpressing KV 6.4. Finally, KV 6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that KV 6.4 can influence human labor pain by modulating the excitability of uterine nociceptors., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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