Effects of gap junction to Ca2+ and to IP3 on the synchronization of intercellular calcium oscillations in hepatocytes

The frequency of free cytosolic calcium concentration ([Ca2+]) oscillations elicited by a given agonist concentration differs between individual hepatocytes. However, in multicellular systems of rat hepatocytes and even in the intact liver, [Ca2+] oscillations are synchronized and highly coordinated. In this paper, we have investigated theoretically the gap junction permeable to calcium and to IP3 on intercellular synchronization by means of a mathematical model, respectively. It is shown that gap junction permeable to calcium and to IP3 are effective on synchronizing calcium oscillations in coupled hepatocytes. Our theoretical results are similar either for the case of Ca2+ acting as coordinating messenger or for the case of IP3 as coordinating messenger. There exists an optimal coupling strength for a pair of connected hepatocytes. Appropriate coupling strength and IP3 level can induce various harmonic locking of intercellular [Ca2+] oscillations. Furthermore, a phase diagram in two-dimensional parameter space of the coupling strength and IP3 level (or the velocity of IP3 synthesis) has been predicted, in which the synchronization region is similar to Arnol'd tongue.