Opposing gates model for voltage gating of gap junction channels

Gap junctions are intercellular channels that link the cytoplasm of neighbo ring cells. Because a gap junction channel is composed of two connexons doc king head-to-head with each other, the channel voltage-gating profile is sy mmetrical for homotypic channels made of two identical connexons (hemichann els) and asymmetric for the heterotypic channels made of two different conn exons (i.e., different connexin composition). In this study we have develop ed a gating model that allows quantitative characterization of the voltage gating of homotypic and heterotypic channels. This model differs from the p resent model in use by integrating, rather than separating, the contributio ns of the voltage gates of the two member connexons. The gating profile can now be fitted over the entire voltage range, eliminating the previous need for data splicing and fusion of two hemichannel descriptions, which is pro blematic when dealing with heterotypic channels. This model also provides a practical formula to render quantitative several previously qualitative co ncepts, including a similarity principle for matching a voltage gate to its host connexon, assignment of gating polarity to a connexon, and the effect of docking interactions between two member connexons in an intact gap junc tion channel.