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Related Experiment Videos

Connexin diversity and gap junction regulation by pHi.

D Francis1, K Stergiopoulos, J F Ek-Vitorín

  • 1Department of Pharmacology, SUNY Health Science Center, Syracuse 13210, USA.

Developmental Genetics
|March 18, 1999
PubMed
Summary
This summary is machine-generated.

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The pH sensitivity of gap junctions depends on connexin type, with alpha 3 and alpha 2 showing higher sensitivity than alpha 1. Interactions between different connexins modify this pH sensitivity, creating functional diversity.

Area of Science:

  • Cellular Biology
  • Biophysics
  • Molecular Biology

Background:

  • Gap junctions mediate direct cell-to-cell communication.
  • Connexins form gap junction channels, and their function can be modulated by intracellular pH (pHi).
  • The specific mechanisms controlling pH-sensitivity in heteromeric gap junctions remain unclear.

Purpose of the Study:

  • To investigate the pH-sensitivity of different connexin types (alpha 3, alpha 2, and alpha 1) in hemichannels and homotypic/heterotypic gap junctions.
  • To determine if pH sensitivity is an intrinsic property of connexins or influenced by interactions within heteromeric channels.
  • To explore the molecular basis for varying pH-dependencies among connexins.

Main Methods:

  • Utilized a proton-sensitive fluorophore to measure intracellular pH (pHi).

Related Experiment Videos

  • Employed electrophysiological techniques to assess electrical coupling in Xenopus oocytes expressing various connexins.
  • Examined hemichannels, homotypic gap junctions, and heterotypic gap junctions formed by alpha 3 (connexin46), alpha 2 (connexin38), and alpha 1 (connexin43).

    • Main Results:

    • Alpha 3 and alpha 2 hemichannels exhibited significant pH sensitivity within the physiological range (pKa values of 7.13 and 7.50, respectively).
    • Homotypic alpha 2 and alpha 3 gap junctions showed pH sensitivity comparable to their respective hemichannels.
    • Alpha 3 and alpha 2 gap junctions were more pH-dependent than alpha 1; heterotypic junction pH sensitivity was not always predictable from individual connexon behavior.
    • Interactions between connexons in heteromeric channels modified pH sensitivity, deviating from simple probabilistic models.

    Conclusions:

    • Dissimilarities in gap junction pH regulation stem from differences in connexin primary sequences.
    • pH regulation is an intrinsic property of connexin hemichannels.
    • Interactions between connexons within heteromeric gap junctions modulate pH sensitivity, contributing to functional diversity.