CaMKII inhibition has dual effects on spontaneous Ca<sup>2+</sup> release and Ca<sup>2+</sup> alternans in ventricular cardiomyocytes from mice with a gain-of-function RyR2 mutation
Mani Sadredini, Marie Haugsten Hansen, Michael Frisk, William E. Louch, Stephan E. Lehnart, Ivar Sjaastad, Mathis K. Stokke
Abstract
Genetically increased RyR2 activity promotes arrhythmogenic Ca 2+ release. Inhibition of CaMKII suppresses RyR2 activity and arrhythmogenic Ca 2+ release. Suppression of RyR2 activity prolongs refractoriness of Ca 2+ release. Prolonged refractoriness of Ca 2+ release leads to arrhythmogenic Ca 2+ alternans. CaMKII inhibition promotes Ca 2+ alternans by prolonging Ca 2+ release refractoriness.
Topics & Concepts
Refractory periodRyanodine receptor 2Internal medicineEndocrinologyChemistryCalciumBiophysicsBiologyRyanodine receptorMedicineCardiac electrophysiology and arrhythmiasIon channel regulation and functionCardiovascular Effects of Exercise