IP3R activity increases propensity of RyR-mediated sparks by elevating dyadic [Ca2＋]

J Chung; A Tilūnaitė; D Ladd; H Hunt; C Soeller; EJ Crampin; ST Johnston; HL Roderick; V Rajagopal

Journal article

IP3R activity increases propensity of RyR-mediated sparks by elevating dyadic [Ca2＋]

J Chung, A Tilūnaitė, D Ladd, H Hunt, C Soeller, EJ Crampin, ST Johnston, HL Roderick, V Rajagopal

Mathematical Biosciences | Published : 2023

DOI: 10.1016/j.mbs.2022.108923

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Abstract

Calcium (Ca2＋) plays a critical role in the excitation contraction coupling (ECC) process that mediates the contraction of cardiomyocytes during each heartbeat. While ryanodine receptors (RyRs) are the primary Ca2＋ channels responsible for generating the cell-wide Ca2＋ transients during ECC, Ca2＋ release, via inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are also reported in cardiomyocytes to elicit ECC-modulating effects. Recent studies suggest that the localization of IP3Rs at dyads grant their ability to modify the occurrence of Ca2＋ sparks (elementary Ca2＋ release events that constitute cell wide Ca2＋ releases associated with ECC) which may underlie their modulatory influence on E..

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University of Melbourne Researchers

Stuart Johnston Author

Vijay Rajagopal Author

Joshua Chung Author

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Awarded by Australian Government

Funding Acknowledgements

This research was supported in part by the Australian Government through the Australian Research Council Discovery Projects funding scheme (project DP170101358) to EJC and VR, the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (project CE140100036) to EJC, the KU Leuven Global PhD Partnerships with The University of Melbourne Grant (GPUM/21/036) to VR and HLR, and The University of Melbourne?s Research Computing Services and the Petascale Campus Initiative. HLR wishes to acknowl-edge financial support through Project Grant G08861N and Odysseus Programme 90663 from the Research Foundation Flanders (FWO) . JC would like to thank Dr Pengxing Cao for the useful discussions on IP3R modelling. STJ is supported by the Australian Research Council (Project No. DE200100988) .