Quantal Ca2+ release and inactivation in a model of the inositol 1,4,5-trisphosphate receptor involving transformation of the ligand by the receptor.

A model explaining quantal Ca2+ release as an intrinsic property of the inositol 1,4,5-triphosphate (IP3) receptor has been put forward. The model is based on the hypothesis that the IP3 receptor can catalyze a transformation of the IP3 molecule differing from its conventional metabolism. A simple kinetic mechanism is considered, in which IP3-induced Ca2+ channel opening is followed by the step of IP3 conversion and channel closure. Examination of the resulting mathematical model shows that it can reproduce well both partial release of stored Ca2+ and the same responsiveness to subsequent IP3 additions. On incorporation of an additional closed state of the channel, the model describes also a time-dependent channel inactivation at a high IP3 dose. Temperature sensitivity of the catalytic step accounts for the reported elimination of quantal responses and inactivation at low temperature. The transformation product is surmised to be a positional or stereo isomer of IP3.