Figure 3. Role of ROS, mitochondrial Na⁺/Ca²⁺ exchange, and CaMKII in maladaptive Ca²⁺ handling induced by elevation of [Na⁺]_i in membrane-permeabilized cardiomyocytes.

A. i) Confocal line-scan image and profile of Ca²⁺ transients in a membrane-permeabilized rabbit ventricular myocyte, recorded during elevation of cytosolic Na⁺ from 5 to 20 mM; ii) spontaneous Ca²⁺ wave frequency and iii) diastolic Ca²⁺ level for the experiment shown in panel (i). B. i, Confocal line-scan image and profile of Ca²⁺ transients in a membrane-permeabilized rabbit ventricular myocyte during elevation of cytosolic Na⁺ from 5 to 20 mM in the presence of the antioxidant CoQ10 (10 μM); ii) spontaneous Ca²⁺ wave frequency and iii) diastolic Ca²⁺ level for the experiment shown in (i). C. Quantification of spontaneous Ca²⁺ wave frequency f/f₀(i) and the diastolic Ca²⁺ level (ii), induced by elevation of [Na⁺]_i in the absence and presence of the antioxidat CoQ10 (10 μM), the CaMKII inhibitor KN-93 (3 μM), the inactive analog KN-92 (3 μM) or mitochondrial Na⁺/Ca²⁺ exchange inhibitor CGP-37157 (CGP, 10 (μM) N=4-10 * p<0.05 vs control; †p<0.05 vs 20 mM Na⁺. f₀, the frequency of spontaneous Ca²⁺ waves at the beginning of experiment.