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Oxford University Press, Cardiovascular Research, 4(111), p. 410-421, 2016

DOI: 10.1093/cvr/cvw173

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Calmodulin/CaMKII inhibition improves intercellular communication and impulse propagation in the heart and is antiarrhythmic under conditions when fibrosis is absent

Journal article published in 2016 by Hiroki Takanari, Vincent J. A. Bourgonje, Magda S. C. Fontes, Antonia J. A. Raaijmakers, Helen Driessen, John A. Jansen, Roel van der Nagel, Bart Kok, Leonie van Stuijvenberg, Mohamed Boulaksil, Yoshio Takemoto, Masatoshi Yamazaki, Yukiomi Tsuji, Haruo Honjo, Kaichiro Kamiya and other authors.
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Aim In healthy hearts, ventricular gap junctions are mainly composed by connexin43 (Cx43) and localize in the intercalated disc, enabling appropriate electrical coupling. In diseased hearts, Cx43 is heterogeneously down-regulated, whereas activity of calmodulin/calcium-calmodulin protein kinase II (CaM/CaMKII) signalling increases. It is unclear if CaM/CaMKII affects Cx43 expression/localization or impulse propagation. We analysed different models to assess this. Methods and results AC3-I mice with CaMKII genetically inhibited were subjected to pressure overload (16 weeks, TAC vs. sham). Optical and epicardial mapping was performed on Langendorff-perfused rabbit and AC3-I hearts, respectively. Cx43 subcellular distribution from rabbit/mouse ventricles was evaluated by immunoblot after Triton X-100-based fractionation. In mice with constitutively reduced CaMKII activity (AC3-I), conduction velocity (CV) was augmented (n = 11, P