Time to Blip—Stochastic Simulation of Single Channel Opening

Abstract

The stochastic dynamics of the inositol-1,4,5-trisphosphate (IP3) receptor (IP3R) is key to understanding a wide range of observed calcium (Ca²⁺) signals. The stochastic nature results from the constant binding and unbinding of Ca²⁺ and IP3 to and from their respective binding sites and is especially important in the initiation of a Ca²⁺ puff (i.e., the release of Ca²⁺ through a cluster of IP3Rs). Once the first IP3R opens, the Ca²⁺ concentration rises significantly around the ion channel, increasing the open probability for neighboring IP3Rs. This opening may trigger the activation of further receptors, giving rise to a Ca²⁺ puff. In this protocol, we determine the time that it takes for a single IP3R to open from rest. We explicitly take into account the tetrameric structure of the IP3R and the fact that multiple subunits must be active before the channel opens. We develop code for a stochastic simulation of the IP3R and simulate it using the software package MATLAB. This protocol shows the basic form of a stochastic simulation algorithm and may serve as a starting point to investigate more complex gating dynamics.