Speaker
Description
Calcium-induced calcium release plays a significant role in mammalian skeletal and cardiac cell excitation. The ion channels responsible for this process are called ryanodine receptors (RyRs), which can exist in several conformational states, including open, closed and inactivated. Transitions between these states are regulated by concentrations of ligands, particularly calcium and magnesium. Recently, Zahradníková and colleagues proposed a structurally-informed allosteric model for this system, that reproduces the steady-state probabilities of RyR channels being open across a range of ligand concentrations~\cite{zahradnikova2025structure}. In this work, we develop a continuous-time Markov chain model for the Closed–Open–Inactivated (COI) gating scheme corresponding to this framework, allowing the kinetic behaviour of RyR channels to be studied beyond steady-state thermodynamics. The model enables the calculation of experimentally observable quantities such as open- and closed-time distributions and burst statistics, providing a link between structural models of RyR regulation and single-channel experimental recordings.
Bibliography
@article{zahradnikova2025structure,
title={Structure-based mechanism of RyR channel operation by calcium and magnesium ions},
author={Zahradn{\'\i}kov{\'a}, Alexandra and Pavelkov{\'a}, Jana and Sabo, Miroslav and Baday, Sefer and Zahradn{\'\i}k, Ivan},
journal={PLOS Computational Biology},
volume={21},
number={4},
pages={e1012950},
year={2025},
publisher={Public Library of Science San Francisco, CA USA}
}
