A physiologic rise in cytoplasmic calcium ion signal increases pannexin1 channel activity via a C-terminus phosphorylation by CaMKII

Significance This work shows that rat and human pannexin1 channels are not intrinsically sensitive to membrane stretch and their activation, previously associated with a physiologic increase in cytoplasmic Ca 2+ concentration, results from phosphorylation via CaMKII in the amino acid residue S394 located in the C terminus of pannexin1. This posttranslational modification does not significantly affect the unitary conductance of the channel but increases the permeability of lateral tunnels to adenosine triphosphate (ATP) and permits the influx of positively charged molecules, such as DAPI, via the external vestibule to the cytoplasm. This activation mechanism might explain the ATP release via pannexin1 channels in diverse cell types under numerous physiologic conditions.