Seminar by Prof. Dirk Gillespie

Rush University Medical Center (Chicago, USA)

Modeling the Ryanodine Receptor ion channel: Single-RyR and RyR-cluster functions

The three isoforms of the Ryanodine Receptor (RyR) ion channel are found in all muscle cells, as well as the brain, neurons, and other tissues. RyR’s role is to conduct Ca²⁺ ions from intracellular stores so that the Ca²⁺ can initiate muscle contraction, among other tissue-specific functions. To do this, each individual RyR protein must select Ca²⁺ over other ions so that a cluster of RyRs can work cooperatively to release large quantities of Ca²⁺ in a short time. Here, the modeling of both single-RyR selectivity/conduction and RyR-cluster function are described. Single-RyR modeling requires atomic-scale physics for which classical Density Functional Theory is used. Cluster-RyR modeling uses reaction-diffusion equations in a complex 3D geometry for which a new algorithm is used to span the vast time and length scales of highly localized Ca²⁺ release diffusing into the cell. Also discussed are how this modeling can potentially be used for RyR-targeted drug screening and drug design.