The connexin channel pore: Pore-lining segments and residues

Connexins form channels with large aqueous pores that mediate flux of ions and biological signaling molecules between cells and across the plasma membrane. Conductance and selectivity properties of connexin channels are diverse. A number of studies have attempted to define the connexin pore in molecular terms and to reveal the key elements of the pore structure that may differ across connexins. These studies include point mutagenesis, domain exchange, scanning cysteine accessibility mutagenesis, and electron cryomicroscopy. Each type of study has provided information that points to specific segments of connexin protein as contributing to the pore lining. However, despite this work, and significant advances in understanding channel structure, gating, and permeation, current views have not reached a consensus regarding the principal domains contributing to the pore.