Poor Prognosis With Coexistence Of EGFR T790M Mutation And Common EGFR-Activating Mutation In Non- Small Cell Lung Cancer

Abstract

It has been shown that IP3R channels are distributed in clusters on the membrane of the endoplasmic reticulum,generating Ca2+ signals on multiple scales from local puffs to global intra- and intercellular waves. Local Ca2+ puffs released from a cluster of IP3R s are strongly stochastic. The most obvious source of noise for puffs is the small number of channels within a cluster. In this chapter we discuss the simulation of stochastic Ca2+ signals. Various simulation methods such as the Gillespie algorithm, a two-state Markovian chain, and gate-based and channel-based Langevin approaches have been introduced for use in the study of stochastic gating dynamics of IP3R channels. Combining the stochastic channel dynamics with the deterministic simulation the Ca2+ diffusion process, the fluctuating Ca2+ signals,including puffs and both intra- and intercellular waves, can be investigated by hybrid models.