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Updated: Dec 14, 2025

Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique
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Voltage-Dependent Potassium Current Recording on H9c2 Cardiomyocytes via the Whole-Cell Patch-Clamp Technique

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Human Labor Pain Is Influenced by the Voltage-Gated Potassium Channel KV6.4 Subunit

Michael C Lee1, Michael S Nahorski2, James R F Hockley3

  • 1University Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.

Cell Reports
|July 23, 2020
PubMed

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 KV6.4-Met419 has a dominant-negative effect and cannot modulate the voltage dependence of KV2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, Kcng4 (KV6.4) expression occurs in 40% of retrograde-labeled mouse uterine sensory neurons, all of which express KV2.1, and over 90% express the nociceptor genes Trpv1 and Scn10a. In neurons overexpressing KV6.4-Met419, the voltage dependence of inactivation for KV2.1 is more depolarized compared with neurons overexpressing KV6.4. Finally, KV6.4-Met419-overexpressing neurons have a higher action potential threshold. We conclude that KV6.4 can influence human labor pain by modulating the excitability of uterine nociceptors.

Keywords:
labor pain, nociception, pain, Kv6.4, quantitative sensory testing, DRG neuron, exome sequencing

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