Related Experiment Videos
Different ionic selectivities for connexins 26 and 32 produce rectifying gap junction channels.
T M Suchyna1, J M Nitsche, M Chilton
1Department of Biological Sciences, SUNY at Buffalo, Buffalo, New York 14260, USA.
Biophysical Journal
|December 10, 1999
Summary
Gap junction channels formed by connexin 26 (Cx26) and connexin 32 (Cx32) exhibit rectifying behavior. This rectification in heterotypic channels is explained by differences in ion selectivity and conductance between Cx26 and Cx32 hemichannels.
Area of Science:
- Cellular Biology
- Biophysics
- Molecular Neuroscience
Background:
- Gap junction channels, formed by connexins, mediate direct cell-to-cell communication.
- Functional diversity of gap junctions is increased by heterotypic interactions between different connexin isoforms.
- Cx26/Cx32 heterotypic channels display significant rectifying behavior, influencing cellular signaling.
Purpose of the Study:
- To determine the channel properties responsible for the rectifying current in Cx26/Cx32 heterotypic gap junction channels.
- To investigate the ion selectivity and conductance characteristics of Cx26 and Cx32 homotypic and heterotypic channels.
- To develop a biophysical model explaining rectification in heterotypic gap junctions.
Main Methods:
- Utilized transfected mouse neuroblastoma 2A (N2A) cells expressing Cx26 and Cx32.
- Measured unitary conductances (gamma(j)) of homotypic and heterotypic channels using patch-clamp electrophysiology.
- Employed anionic substitution (glutamate for Cl-) to assess charge selectivity.
- Developed a biophysical model based on Nernst-Planck and Poisson equations.
Main Results:
- Cx26 homotypic channels showed higher unitary conductance (135 pS) and cation preference compared to Cx32 homotypic channels (53 pS).
- Cx26/Cx32 heterotypic channels exhibited significant rectification, with conductance increasing by 2.9-fold as voltage polarity shifted.
- The developed biophysical model predicted rectification in heterotypic channels, attributing it to asymmetries in hemichannel properties.
Conclusions:
- Rectification in Cx26/Cx32 heterotypic gap junctions arises from distinct ion selectivity and conductance properties of Cx26 and Cx32 hemichannels.
- Asymmetries in hemichannel conductance/permeability, modeled as Donnan potentials, lead to ion accumulation/depletion and voltage-dependent rectification.
- Understanding these properties is crucial for comprehending intercellular communication and its modulation by connexin composition.