Inositol 1,4,5-trisphosphate directly opens diphtheria toxin channels

Inositol 1,4,5-trisphosphate (IP3) is a soluble second messenger, which acts by cooperatively releasing Ca2+ into the cytosol from non-mitochondrial stores, probably by activating Ca(2+)-permeable channels. We demonstrate that submicromolar concentrations of IP3 can directly open the Ca(2+)-permeable diphtheria toxin channel, and that this occurs by IP3 binding to a specific site on the toxin protein. This provides a model for IP3-induced Ca2+ release and suggests that IP3-induced channel opening may play a role in diphtheria intoxication and in protein translocation across membranes.