Figure 3. Sarcoplasmic reticulum (SR) Ca²⁺ leak and spontaneous SR Ca²⁺-release events (SCaEs).

A, Experimental protocol employing tetracaine (1-mmol/L) to block RyR2 under 0-mmol/L extracellular Na⁺/Ca²⁺ to block sarcolemmal Ca²⁺-fluxes (left). The decrease in fluorescence in response to tetracaine shown in the example is proportional to SR Ca²⁺-leak.³⁶ Subsequently, the amplitude of the caffeine-induced Ca²⁺-transient was used to assess SR Ca²⁺-load. Right panel shows SR Ca²⁺-leak/SR Ca²⁺-load ratio in Ctl and POAF. Individual leak and load components are shown in Online Figure VIII. B-C, Examples (B) and quantification (C) of SCaEs occurring prior to tetracaine application in the absence of sarcolemmal Ca²⁺-fluxes at −80 mV in Ctl and POAF. D-E, Examples (D) and quantification (E) of spontaneous I_NCX resulting from SCaEs (at −50 mV) in perforated-patch experiments in an independent cohort of Ctl and POAF cardiomyocytes. N-numbers indicate numbers of cardiomyocytes/patients. *P<0.05 vs. Ctl based on multilevel models with log-transformed data.