Effects of gap junction to Ca 2+ and to IP 3 on the synchronization of intercellular calcium oscillations in hepatocytes

Abstract

The frequency of free cytosolic calcium concentration ([Ca 2+]) oscillations elicited by a given agonist concentration differs between individual hepatocytes. However, in multicellular systems of rat hepatocytes and even in the intact liver, [Ca 2+] oscillations are synchronized and highly coordinated. In this paper, we have investigated theoretically the gap junction permeable to calcium and to IP 3 on intercellular synchronization by means of a mathematical model, respectively. It is shown that gap junction permeable to calcium and to IP 3 are effective on synchronizing calcium oscillations in coupled hepatocytes. Our theoretical results are similar either for the case of Ca 2+ acting as coordinating messenger or for the case of IP 3 as coordinating messenger. There exists an optimal coupling strength for a pair of connected hepatocytes. Appropriate coupling strength and IP 3 level can induce various harmonic locking of intercellular [Ca 2+] oscillations. Furthermore, a phase diagram in two-dimensional parameter space of the coupling strength and IP 3 level (or the velocity of IP 3 synthesis) has been predicted, in which the synchronization region is similar to Arnol'd tongue.