MECHANISM OF CA-RETICULUM - A COMPUTER-MODEL(+ RELEASE FROM THE SARCOPLASMIC)

The proposed model describes myocyte calcium (Ca++) cycling, emphasizi ng the kinetics of sarcoplasmic reticulum (SR) Ca++ release channels. The suggested SR channel regulating mechanism includes two types of Ca ++ binding sites: (1) low affinity sites with high binding rates, regu lating the opening of Ca++ channels and (2) high affinity sites with l ow binding rates, which regulate their closing. The amount of Ca++ rel eased from the SR and the peak value of Ca++ ion concentration [Ca++] in the cytoplasm were found to depend on the rate of the increase of [ Ca++], similar to Ca++ induced Ca++ release experiments. The model des cribes spontaneous release of Ca++ from overloaded SR. The dependence of the control mechanism on the activating and inactivating sites is s ubstantiated by simulations of ryanodine intervention, providing resul ts similar to experimental results. Simulations under conditions of is olated SR vesicles produced Ca++ release results similar to measured d ata. Consequently, it is suggested that the recovery of Ca++ release c hannels represents the rate limiting factor in the process of mechanic al restitution. (C) 1998 Biomedical Engineering Society.