Decoding Connexin Hemichannels: Structure, Function, and Regulatory Mechanisms

Isaac E García1,2, Jorge E Contreras3

  • 1Laboratorio de Fisiología Molecular y Biofísica, Facultad de Odontología, Universidad de Valparaíso, Valparaíso, Chile.

Annual Review of Physiology
|November 11, 2025
PubMed

Insights

Connexin hemichannels facilitate cellular communication and are implicated in diseases. This review explores their function, regulation, and therapeutic potential.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Physiology

Background:

  • Connexin hemichannels are crucial for cell-to-cell communication, ion, and metabolite transport.
  • Their roles in disease are known, but physiological functions require further investigation.
  • Mechanisms of hemichannel gating, permeation, and regulation are not fully understood.

Purpose of the Study:

  • To review recent advancements in understanding connexin hemichannel function.
  • To explore molecular determinants of hemichannel opening, closing, and regulation.
  • To highlight therapeutic potential in various disease contexts.

Main Methods:

  • Literature review of foundational insights and recent advancements.
  • Analysis of molecular mechanisms governing hemichannel gating and permeation.
  • Integration of findings on structural adaptations and signaling interactions.

Main Results:

  • Hemichannel function is linked to cellular signaling networks.
  • Structural adaptations modulate hemichannel permeation and gating.
  • Emerging concepts in hemichannel regulation are identified.

Conclusions:

  • Connexin hemichannels play vital roles in tissue homeostasis and cellular signaling.
  • Further understanding of hemichannel regulation is critical.
  • Connexin hemichannels represent promising therapeutic targets for diseases.

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