Enhanced Late I Induces Intracellular Ion Disturbances and Automatic Activity in the Guinea Pig Pulmonary Vein Cardiomyocytes.

The effects of enhanced late I, a persistent component of the Na channel current, on the intracellular ion dynamics and the automaticity of the pulmonary vein cardiomyocytes were studied with fluorescent microscopy. Anemonia viridis toxin II (ATX- II), an enhancer of late I, caused increases in the basal Na and Ca concentrations, increases in the number of Ca sparks and Ca waves, and the generation of repetitive Ca transients. These phenomena were inhibited by eleclazine, a blocker of the late I; SEA0400, an inhibitor of the Na/Ca exchanger (NCX); H89, a protein kinase A (PKA) inhibitor; and KN-93, a Ca/calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results suggest that enhancement of late I in the pulmonary vein cardiomyocytes causes disturbance of the intracellular ion environment through activation of the NCX and Ca-dependent enzymes. Such mechanisms are probably involved in the ectopic electrical activity of the pulmonary vein myocardium.