Patch clamp recordings enable us to watch a single inositol-trisphosphate receptor (IP3R) in action. At first glance we only see that the IP3R opens and closes stochastically but a closer look reveals that the channel alternates between two different levels of activity – a highly active mode where the IP3R opens and closes frequently and a nearly inactive mode in which the channel is mostly closed. Applying statistical change point analysis to the most comprehensive single channel data set currently available highlights the importance of this observation: We find that the dynamics of the IP3R is entirely regulated by switching between these two modes. In order to build a mathematical model based on this underlying principle the hierarchical Markov model is developed and then fitted to type 1 and type 2 IP3R data for a wide range of concentrations of IP3R, Ca2+ and ATP. I will present this model and will especially emphasize the insights in the biophysics of the IP3R that were gained along the way.
