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.