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. 2020 Jan 29;10:1632. doi: 10.3389/fphar.2019.01632

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Copyright © 2020 Kohajda, Tóth, Szlovák, Loewe, Bitay, Gazdag, Prorok, Jost, Levijoki, Pollesello, Papp, Varró and Nagy

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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The potential influence of Ca²⁺ handling suppression by 5 µM ryanodine (RYA) (green line) and 1 µM ORM-10962 (red line) on the effect of funny current (I_f) reduction was investigated. As representative curves panel (A) and diagram panel (B) report, both drugs increased the cycle length (CL) of the action potential. Statistical analysis was achieved by ANOVA. * means RYA compared to control, $ means ORM-10962 (ORM) compared to RYA, and # means ivabradine (IVA) compared to ORM. Comparison of the effect of 3 µM IVA on the CL under normal condition (i.e., without any other inhibitors) and after 5 µM RYA + 1µM ORM shows that the same dose of IVA has markedly increased effect when the contribution of Na+/Ca2+ exchanger (NCX) is reduced by concomitant application of RYA and ORM panel (C).