QUANTAL CA2-TRISPHOSPHATE RECEPTOR INVOLVING TRANSFORMATION OF THE LIGAND BY THE RECEPTOR( RELEASE AND INACTIVATION IN A MODEL OF THE INOSITOL 1,4,5)

A model explaining quantal Ca2+ release as an intrinsic property of th e inositol 1,4,5-trisphosphate (IP3) receptor has been put forward. Th e model is based on the hypothesis that the IP3 receptor can catalyze a transformation of the IP3 molecule differing from its conventional m etabolism. A simple kinetic mechanism is considered, in which IP3-indu ced Ca2+ channel opening is followed by the step of IP3 conversion and channel closure. Examination of the resulting mathematical model show s that it can reproduce well both partial release of stored Ca2+ and t he same responsiveness to subsequent IP3 additions. On incorporation o f 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 eliminatio n of quantal responses and inactivation at low temperature. The transf ormation product is surmised to be a positional or stereo isomer of IP 3.