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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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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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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
Summary

Genetic factors influence labor pain. A specific KCNG4 gene variant (KV6.4-Met419) affects uterine sensory neuron excitability, potentially increasing pain perception during childbirth.

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

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Area of Science:

  • Neuroscience
  • Genetics
  • Pain Research

Background:

  • Investigating genetic influences on labor pain is crucial for understanding pain modulation.
  • Identifying specific genes and their variants associated with pain perception can lead to targeted interventions.

Purpose of the Study:

  • To explore the genetic basis of labor pain in women who do not require analgesia.
  • To identify genetic variants in KCNG4 associated with pain sensitivity during childbirth.

Main Methods:

  • Studied healthy women with no labor analgesia request, assessing sensory and psychometric data.
  • Analyzed genetic variations, specifically SNP rs140124801 in KCNG4, and its rare allele.
  • Utilized in vitro and in vivo models to examine the functional effects of KCNG4 variants on neuronal excitability.

Main Results:

  • An excess of heterozygotes for the rare KCNG4 allele (rs140124801) was observed.
  • The KV6.4-Met419 variant demonstrated a dominant-negative effect, impairing KV2.1 function.
  • KCNG4 expression was found in mouse uterine sensory neurons co-expressing KV2.1, Trpv1, and Scn10a.
  • Neurons overexpressing KV6.4-Met419 exhibited altered KV2.1 inactivation and a higher action potential threshold.

Conclusions:

  • KCNG4, specifically the KV6.4 subunit, plays a role in modulating uterine nociceptor excitability.
  • The KV6.4-Met419 variant may influence human labor pain by altering neuronal firing properties.