Self-regulated Processes: applications to the IP3 receptor.

SILVINA PONCE DAWSON; DANIEL E. FRAIMAN BORRAZAS; BERNARDO PANDO

Long Beach, CA, USA

Congreso; Biophysical Society 49th Annual Meeting; 2005

Biophysical Society

In most ion channel models, channels switch stochastically between a discrete set of states. Usually it is assumed that the switching is represented by a Markov process that is hidden since the transition between different closed states cannot be observed directly in patch-clamp experiments. This type of description gets increasingly complicated when one tries to describe the dynamics of clusters of channels, like those that occur in the oocyte, where IP3 receptors are highly clusterized. Ca2+ release from a subset of channels in a cluster is the building block of Ca2+ signals in this cell type. But since the IP3 receptor is mainly a Ca2+ channel and Ca2+ is one of its agonists, coupling the description of the cluster to the intracellular Ca2+ dynamics seems unavoidable. We propose here an alternative approach, in which the transition from a state not only depends on the state, but also on the duration during which the system remained on that state. We call this a self-regulated process. We show how a simple two state model can give rise to complex behaviors such as gating modes and bursting activity and present a way of testing if the realization of a stochastic process comes from a self-regulated process. We finally show a simplified description of a cluster of IP3 receptors using this approach.