InsP3R-RyR channel crosstalk augments sarcoplasmic reticulum Ca2 release and arrhythmogenic activity in post-MI pig cardiomyocytes

X Jin; A Meletiou; J Chung; A Tilunaite; K Demydenko; E Dries; RD Puertas; M Amoni; A Tomar; G Gilberta; P Claus; C Soeller; V Rajagopal; K Sipido; HL Roderick

Journal article

InsP3R-RyR channel crosstalk augments sarcoplasmic reticulum Ca2 release and arrhythmogenic activity in post-MI pig cardiomyocytes

X Jin, A Meletiou, J Chung, A Tilunaite, K Demydenko, E Dries, RD Puertas, M Amoni, A Tomar, G Gilberta, P Claus, C Soeller, V Rajagopal, K Sipido, HL Roderick

Journal of Molecular and Cellular Cardiology | ELSEVIER SCI LTD | Published : 2023

DOI: 10.1016/j.yjmcc.2023.03.015

Abstract

Ca2+ transients (CaT) underlying cardiomyocyte (CM) contraction require efficient Ca2+ coupling between sarcolemmal Ca2+ channels and sarcoplasmic reticulum (SR) ryanodine receptor Ca2+ channels (RyR) for their generation; reduced coupling in disease contributes to diminished CaT and arrhythmogenic Ca2+ events. SR Ca2+ release also occurs via inositol 1,4,5-trisphosphate receptors (InsP3R) in CM. While this pathway contributes negligeably to Ca2+ handling in healthy CM, rodent studies support a role in altered Ca2+ dynamics and arrhythmogenic Ca2+ release involving InsP3R crosstalk with RyRs in disease. Whether this mechanism persists in larger mammals with lower T-tubular density and coupli..

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University of Melbourne Researchers

Vijay Rajagopal Author

Joshua Chung Author

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Grants

Awarded by Australian Government

Funding Acknowledgements

This work was supported by the Fund for Scientific Research-Flanders (FWO projects G.0617.09 and G.0918.15 to KRS, FWO Project grant G08861N and FWO Odysseus Project 90663 to HLR; FWO postdoctoral fellowships to ED and GG; FWO PhD fellowship to MA). CS' contributions were supported by the Human Frontier Science Program (No. 0027/2013), the Engineering and Physical Sciences Research Council of the UK (No. EP/N008235/1) and Biotechnology and Biological Sciences Research Council Grants BB/P026508/1 and BB/T007176/1. This research was supported in part by the Australian Government through the Australian Research Council Discovery Projects funding scheme (project DP170101358) to VR. We thank Patricia Holemans and Roxane Menten for technical assistance and Dr. Alexander Clowsley for assistance in preparation and staining of cardiac tissue for DNA-PAINT analysis.