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Description

Calcium is a very common messenger in many biological systems. Calcium signaling inside cells is often mediated by calcium-gated calcium channels such as inositol 1,4,5-triphosphate recpetors (IP3R) and ryanodine receptors (RyR) located on internal calcium stores. There is a characteristic isoform expression of IP3Rs and RyRs associated with distinct cell types and this variation is thought to contribute to the diversity of calcium signaling. Although many previous theoretical studies have investigated the dynamics of localized calcium release sites, so far all such studies focused on release sites consisting of identical channels. We have extended an existing mathematical model to release sites with two (or more) receptor types, each with its distinct channel kinetics. Mathematically, the release site is represented by a transition probability matrix that is coupled to a dynamically changing calcium domain. We use this model to investigate the role of calcium inactivation in release site dynamics, particularly in the termination of synchronous channel activity. We show that the release site dynamics depend sensitively not only on the fraction of channels without calcium inactivation, but their spatial position.