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. 2021 Sep 24;12:732573. doi: 10.3389/fphys.2021.732573

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Copyright © 2021 Lyon, van Opbergen, Delmar, Heijman and van Veen.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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(A) Representation of the intracellular calcium transient, RyR2 configuration (inactive, recovery and open state), cleft calcium levels and RyR2-mediated calcium release in the wildtype model (blue) and PKP2-cKO model with BARS (1.5-fold Cx43 hemichannel-mediated calcium influx incorporated) (purple). Bottom: Zoom-in on the zone of DAD occurrence. (B) Percentage of models showing DAD-like events when comparing PKP2-cKO model with no Cx43 hemichannel-mediated calcium influx with and without BARS, with or without reduced RyR2 affinity, PKP2-cKO model plus BARS (1.5-fold Cx43 hemichannel-mediated calcium influx incorporated), with or without reduced RyR2 affinity, as well as the PKP2-cKO model plus BARS and 2.5-fold Cx43 hemichannel-mediated calcium influx, with or without reduced RyR2 affinity. (C) Representative calcium transient traces of the different models. Please note the disappearance of DADs when reducing the RyR2 calcium affinity in the PKP2-cKO model in presence BARS (1.5-fold Cx43 hemichannel-mediated calcium influx still incorporated).