http://www.vimm.it/cochlea). These cells are thought to ferry K+ away from sensory cells, thus preventing opening of channels in these cells that would admit toxic levels of Ca2+.
Most connexin mutations associated with deafness yield missorted or nonfunctional channel proteins. The Italian group focused on the V84L mutant, which is correctly sorted and, as they show, forms channels with normal unitary conductance and open channel probabilities. Ions and the higher molecular weight dye Lucifer yellow can pass through these channels.
But IP3 introduced into cells expressing V84L mutant connexins did not, as in wild type, generate Ca2+ waves in adjacent cells. Failure to spread this message may be the basis for a failure in K+ scavenging and thus sensory cell death.
Thus the addition of a single CH2 unit can determine the difference between conductance and nonconductance of IP3. The detailed structure of the relevant connexin is not yet known, but the minimal structural difference may be amplified if the residue in question pokes into the channel that is formed by 6 connexin subunits.