TEMPERATURE EFFECTS ON THE STOCHASTIC GATING OF THE IP3R CALCIUM RELEASE CHANNEL: A NUMERICAL SIMULATION STUDY

摘要

The importance of the kinetic study of endoplasmatic calcium ion channels in different intracellular processes is known today. Although there are few experimental reports on the temperature dependency of IP3R channel functions, we did not find any detailed theoretical study on this subject. For this purpose, we used a modified Gillespie algorithm to investigate the effect of temperature on the conditions affecting the open state of a single subunit of the De Young-Keizer (DYK) model. Population of the states was considered as the subject of fluctuation. Key features of the channel, such as bell-shaped dependency of open probability to the Calcium concentrations were modeled at different temperatures, too. The range of temperature variation was selected by regarding the experimental data on IP3R channel. By increasing the temperature, we had the very slow time domains (t: 10(-1) s) and the much slower time domains (t: 10(0) s) in addition to other time domains, which could be seen as new time categories in InsP3R studies, and so the results were reported in these time domains, as well. We found out that increase in temperature declined the open probability in some concentrations of Ca2+ and/or IP3. Also, by introducing the intensity graphs, broadening of the range of fluctuations and lowering of the order of frequency of fluctuations for the population of each state were observed due to the temperature increments. The temperature effects on the activation and inactivation states of the channel were studied in the framework of the reaction paths. We did not find similar paths at different time domains; several paths observed which were totally different all together. These time-dependent reaction paths are also depending on the Ca2+ and/or the IP3 concentrations. So, one can predict the most probable reaction paths at different concentrations and temperatures and also determine which kind of the path it is; a path for closing the channel or a path to open it. Finally, the temperature effects on the calcium inhibited states were studied. We found out that calcium ion inhibitions were shifted to lower calcium concentration by increasing the temperature. The results suggests that inhibiting role of calcium is not only [Ca2+] and/or [IP3] dependent, but also temperature dependent.