CaMKII inhibition has dual effects on spontaneous Ca2+ release and Ca2+ alternans in ventricular cardiomyocytes from mice with a gain-of-function RyR2 mutation-Reference-Cited by-同舟云学术

CaMKII inhibition has dual effects on spontaneous Ca2+ release and Ca2+ alternans in ventricular cardiomyocytes from mice with a gain-of-function RyR2 mutation

Published:2021-08-01 Issue:2 Volume:321 Page:H446-H460
ISSN:0363-6135
Container-title:American Journal of Physiology-Heart and Circulatory Physiology
language:en
Short-container-title:American Journal of Physiology-Heart and Circulatory Physiology

Author:

Sadredini Mani¹²^ORCID,Haugsten Hansen Marie¹²,Frisk Michael¹²,Louch William E.¹²,Lehnart Stephan E.³⁴⁵^ORCID,Sjaastad Ivar¹²^ORCID,Stokke Mathis Korseberg¹²⁶^ORCID

Affiliation:

1. Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway

2. KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway

3. Department of Cardiology and Pulmonology, Heart Research Center Göttingen, University Medical Center Göttingen, Göttingen, Germany

4. Cluster of Excellence “Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells” (MBExC), University of Göttingen, Göttingen, Germany

5. DZHK (German Centre for Cardiovascular Research), Göttingen, Germany

6. Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway

Abstract

Genetically increased RyR2 activity promotes arrhythmogenic Ca2+ release. Inhibition of CaMKII suppresses RyR2 activity and arrhythmogenic Ca2+ release. Suppression of RyR2 activity prolongs refractoriness of Ca2+ release. Prolonged refractoriness of Ca2+ release leads to arrhythmogenic Ca2+ alternans. CaMKII inhibition promotes Ca2+ alternans by prolonging Ca2+ release refractoriness.

Funder

South-Eastern Norway Regional Health Authority

Olav Raagholt and Gerd Meidel Raagholt's Foundation

Rakel and Otto-Kristian Bruun's Endowment

The Blix Family Foundation for Promotion of Medical Research

Deutsche Forschungsgemeinschaft

Simon Fougner Hartmanns Familiefond

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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