Permeability of connexin channels

Because of the diversity of connexin isoforms and their combinations that can compose connexin channels, there is large diversity in the permeability properties of the channels. Unlike most ion channels, the relevant permeabilities extend from charge selectivity among atomic ions such as K⁺ and Ca²⁺, through the size and charge selectivity among nonbiological tracer molecules, to highly specific selectivities among cytoplasmic molecules. Distinct experimental approaches are used to define each of these types of selectivity. In general, permeability to current-carrying atomic ions is high, but is substantially charge-selective in some cases. In general, there is permeability to molecular tracers up to ∼800 Da, with some channels having significantly lower cutoff thresholds, influenced by charge. Permeability to cytoplasmic molecules is less well explored, but seems to be highly variable and specific, often violating the size and charge selectivities suggested by studies using nonbiological tracers. The unitary channel conductances and the molecular permeabilities to tracer molecules and to cytoplasmic molecules do not correlate well with each other, and do not allow easy inferences or extrapolations about what biological molecules can permeate any particular form of connexin channel, and how well. In spite of this, even the sparse data obtained to date on cytoplasmic permeants gives clues as to the roles that connexin-specific permeabilities may play in biology.