Emerging issues of connexin channels: biophysics fills the gap

  title={Emerging issues of connexin channels: biophysics fills the gap},
  author={Andrew L. Harris},
  journal={Quarterly Reviews of Biophysics},
  pages={325 - 472}
  • A. Harris
  • Published 1 August 2001
  • Biology
  • Quarterly Reviews of Biophysics
1. Introduction 326 1.1 What? Terminology and general properties 327 1.2 Why? Reasons for biophysical study 329 1.3 How? Special issues for study of connexin channels 330 2. Molecular and structural context 331 2.1 Biochemical features 331 2.2 Structures 334 2.2.1 Junctional channels 335 2.2.2 Hemichannels 338 2.2.3 Heteromeric channels 342 2.2.4 Junctional plaques 347 3. Experimental approaches and issues specific to study of connexin channel physiology 349 3.1 Macroscopic currents 349 3.1.1… 

Structure of the connexin 26 gap junction channel at 3.5 Å resolution

The crystal structure of the gap junction channel formed by human connexin 26 (Cx26), also known as GJB2, is reported at 3.5 Å resolution, and structural determinants of solute transport through the channel are discussed.

Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel

Structural insights into the permeant selectivity of Cx31.3 hemichannel are provided, which shows substantial structural changes of highly conserved regions in the connexin family, including opening of calcium ion–binding tunnels, reorganization of salt-bridge networks, exposure of lipid-binding sites, and collocation of amino-terminal helices at the cytoplasmic entrance.

Characterization of Zebrafish Cx43.4 Connexin and its Channels

The biochemical and immunohistochemical characterization of zebrafish connexin zfCx43.4, an orthologue of mammalian and avian Cx45, and the electrophysiological properties of junctional channels formed by this protein are reported on.

Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate

The results show that PtdIns(4,5)P2 is a key regulator of Cx43 channel function, with no role for other second messengers, and suggest that ZO-1 assembles PLCβ3 and Cx 43 into a signaling complex to allow regulation of cell–cell communication by localized changes in Ptdins 4,5]P2.

A biophysical approach to the study of structure and function of connexin channel nanopores

This method permits quantification of defects of metabolic coupling and can be used to investigate interdependence of intercellular diffusion and cross-talk between diverse signalling pathways.

Cosegregation of permeability and single-channel conductance in chimeric connexins.

To test which parts of the channels formed by connexins determine the exclusion limit for the transit of molecules in the size range of second messengers and metabolites, a domain exchange approach was used in combination with an accessibility assay for nonelectrolytes and flux measurements, suggesting that two open hemichannel forming connex Ins differ in accessibility and permeability.

Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule

The electron crystallographic structure of a human Cx26 mutant (M34A) is reported to suggest that the two docked hemichannels can be independent and may regulate their activity autonomously with a plug in the vestibule.

Structure and closure of connexin gap junction channels


Results obtained largely from studies of hemichannels that demonstrate that the channel pore is narrowed down, but not closed, by protein kinase C-mediated phosphorylation of a single site, serine 368, located 14 residues away from the C-terminal end of connexin 43.

Voltage-dependent gating of the Cx32*43E1 hemichannel: Conformational changes at the channel entrances

The results presented here combined with previous studies suggest that the loop-gate permeability is essentially focal, in that conformational changes in the parahelix but not the intracellular entrance are sufficient to prevent ion flux.



Selective permeability of different connexin channels to the second messenger inositol 1,4,5-trisphosphate.

The notion that diffusion of inositol 1,4,5-trisphosphate through connexin32-containing gap junctions is essential for the optimal physiological response, for example by recruiting liver parenchymal cells that contain subthreshold levels of this short lived second messenger, is supported.

Size Selectivity Between Gap Junction Channels Composed of Different Connexins

A graded series of neutral polyethylene glycol probes (PEGs), which eliminate charge contribution completely, are used to specifically assess the physical exclusion limits of gap junction channels formed by different connexins.

Properties and regulation of gap junctional hemichannels in the plasma membranes of cultured cells

It is concluded that Cx43 hemichannels are found in the plasma membrane, where they are regulated by multiple signaling pathways, and likely represent an important stage in gap junction assembly.

Human connexin 43 gap junction channel gating: evidence for mode shifts and/or heterogeneity.

The gating parameters of human connexin 43 (Cx43) gap junction channels were determined using dual whole cell patch clamp and methods designed for analysis of multichannel recordings and provided evidence for a homogeneous population of Cx43 channels, which can mode shift under the influence of voltage.

Gating of cx46 gap junction hemichannels by calcium and voltage

The gate that closes hemichannels in response to increased calcium concentration with whole-cell and single-channel records is characterized and it is suggested that the cx46 gap junction hemichannel may exert a physiological function in the lens.

Properties of channels from rat liver gap junction membrane fractions incorporated into planar lipid bilayers.

The results further support the idea that functional connexin32 gap junction channels are present in channel activity recorded from rat liver junctional membranes incorporated into planar bilayers.