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. 2021 May 11;12:656516. doi: 10.3389/fphys.2021.656516

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Copyright © 2021 Wang, Myles, Lee, Bers and Ripplinger.

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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Inhibition of sarco-endoplasmic reticulum Ca²⁺-ATPase (SERCA) with cyclopiazonic acid (CPA) promoted the emergence of spatially discordant alternans at slower pacing cycle lengths (PCL). (A) Magnitude of sarcoplasmic reticulum (SR) Ca²⁺ alternans at progressively faster PCLs. Spatial discordance emerges at 220-ms PCL for 10 μM of CPA and at 200-ms PCL for 5 μM CPA, while baseline and 1 μM of CPA remain spatially concordant over the PCLs shown. (B) Alternans phase with the nodal line indicated in white where alternans transitions from small:large to large:small. Optical V_m and SR Ca²⁺ traces are from the regions indicated with white and black boxes. (C) Pacing threshold for the induction of spatial discordance was significantly increased with CPA. Mean ± SD. N = 3 (*p < 0.05 vs. baseline).