Proceedings of the 3rd Federation of European Physiological Societies (FEPS) pages:83-86
3rd Congress of the Federation-of-European-Physiological-Societies edition:3 location:Nice, France date:Jun 28-Jul 02, 2003
We constructed a deletion mutant of the mouse inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) type I lacking its first 225 aa (Delta1-225), which act as a suppressor of IP3 binding. IP3 binding to the deletion mutant could not be stimulated by thimerosal (TMS). Within the N-terminus of the IP3R we demonstrated an interaction between aa 1225 and 226-604, which was strengthened by both TMS and Ca2+. In the presence of TMS, calmodulin weakened the interaction. Mutation of two well-conserved cysteines mimicked the stimulatory effect of TMS. Using a unidirectional Ca-45(2+)-flux technique we showed that the bellshaped activation of IP3-induced Ca2+-release (IICR) by TMS was shifted to lower concentrations in the presence of Ca2+. These data suggest that Ca2+ and TMS synergistically regulate the IP3R type 1 function.