Destabilized Calcium Dynamics Visualized Using the Genetically-coded Probe GCaMPJ in Intact Hearts of Calstabin-null Mice

Optical imaging of intracellular calcium ions (Ca2+) using Ca2+-sensitive dyes or genetically encoded Ca2+ indicators (GECIs) offers high spatial and temporal resolution, and has revealed several critical mechanisms of Ca2+ signaling in cardiomyocytes. However, little progress has been made in the imaging of global Ca2+ events in intact mammalian hearts. Here, transgenic mice with cardiac-specific expression of GCaMPJ were generated, a new GECI with an overall enhancement in the sensitivity of Ca2+ dynamics compared to previous GCaMPs. Primarily, no cardiotoxicity was detected in the transgenic mice with cardiac-specific expression of GCaMPJ. GCaMPJ also showed superiority in indicating Ca2+ dynamics, and spiral and ripple waves of Ca2+ dynamics were detected in the intact hearts. The transgenic mice confirmed the function of the calstabin protein in modulating Ca2+ cycling in the integrated heart and further demonstrated that pharmacological stabilization of the ryanodine receptor (RyR) can prevent arrhythmias involving chaotic Ca2+ events.