Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel Kv6.4 Subunit
Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel Kv6.4 Subunit
复制标题
DOI：
10.1016/j.celrep.2020.107941
复制
发表时间：
2020-07-21
期刊：
影响因子：
8.8
通讯作者：
Woods, C. Geoffrey
中科院分区：
文献类型：
--
作者：
Lee, Michael C.;Nahorski, Michael S.;Woods, C. Geoffrey
通过研究在第一次分娩时不需要镇痛的健康女性，我们调查了遗传对分娩疼痛的影响。这些女性的感觉和心理测试结果正常，但袖带压力疼痛明显较高。我们在 KCNG4 中发现过量携带 SNP rs140124801 罕见等位基因的杂合子。罕见的变异体 K(v)6.4-Met419 具有显性负效应，并且不能调节 K(v)2.1 失活的电压依赖性，因为它无法运输到质膜。在体内，Kcng4 (K(v)6.4) 表达出现在 40% 逆行标记的小鼠子宫感觉神经元中，所有这些神经元都表达 K(v)2.1，超过 90% 表达伤害感受器基因 Trpv1 和扫描10a。在过表达 K(v)6.4-Met419 的神经元中，与过表达 K(v)6.4 的神经元相比，K(v)2.1 失活的电压依赖性更加去极化。最后，K(v)6.4-Met419 过表达神经元具有更高的动作电位阈值。我们得出结论，K(v)6.4 可以通过调节子宫伤害感受器的兴奋性来影响人类分娩疼痛。
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.