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Heterotypic docking of Cx43 and Cx45 connexons blocks fast voltage gating of Cx43

S Elenes1, A D Martinez, M Delmar

  • 1Krannert Institute of Cardiology, Indiana University, Indianapolis, Indiana 46202, USA.

Biophysical Journal
|August 18, 2001
PubMed

Insights

Connexin 43 (Cx43) and connexin 45 (Cx45) form heterotypic channels with unique voltage-gating properties. Docking Cx43 and Cx45 reveals Cx43

Area of Science:

  • Cellular Biology
  • Biophysics
  • Molecular Biology

Background:

  • Connexins (Cxs) form gap junctions, enabling intercellular communication.
  • Distinct connexin subtypes co-localize, suggesting heteromultimeric channel formation.
  • Understanding heterotypic channel gating is crucial for cellular signaling.

Purpose of the Study:

  • To investigate the voltage-gating properties of heterotypic channels formed by connexin 43 (Cx43) and connexin 45 (Cx45).
  • To determine the influence of heterotypic Cx43-Cx45 channel formation on connexon gating kinetics and conductance.
  • To elucidate the role of the Cx43 carboxyl-terminal domain in heterotypic channel function.

Main Methods:

  • Transfection of N2A neuroblastoma or HeLa cells with Cx43 or Cx45 DNA.
  • Utilizing a double whole-cell voltage-clamp technique to assess channel properties.
  • Analysis of macroscopic and single-channel gating kinetics and conductance.

Main Results:

  • Cx43-Cx45 heterotypic channels exhibit rectification, with rapid inactivation of Cx45 connexons under hyperpolarizing pulses.
  • Cx43 connexons in heterotypic channels show significantly slower inactivation kinetics during depolarizing pulses compared to homotypic Cx43 channels.
  • Main conductance of heterotypic channels is additive and voltage-independent, with no detectable residual conductance.

Conclusions:

  • The Cx43 carboxyl-terminal domain plays a role in fast gating and residual conductance, which is potentially inhibited by heterotypic docking.
  • Heterotypic docking of Cx43 and Cx45 may induce conformational changes affecting channel gating mechanisms.
  • These findings provide insights into the complex regulation of intercellular communication through heteromeric gap junctions.

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