Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel K_V6.4 Subunit.

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_V6.4-Met419 has a dominant-negative effect and cannot modulate the voltage dependence of K_V2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, Kcng4 (K_V6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express K_V2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a. In neurons overexpressing K_V6.4-Met419, the voltage dependence of inactivation for K_V2.1 is more depolarized compared with neurons overexpressing K_V6.4. Finally, K_V6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that K_V6.4 can influence human labor pain by modulating the excitability of uterine nociceptors.

SUBMITTER: Lee MC 

PROVIDER: S-EPMC7383234 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature