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

The effects of enhanced late I _Na , 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 _Na , caused increases in the basal Na ⁺ and Ca ²⁺ concentrations, increases in the number of Ca ²⁺ sparks and Ca ²⁺ waves, and the generation of repetitive Ca ²⁺ transients. These phenomena were inhibited by eleclazine, a blocker of the late I _Na ; SEA0400, an inhibitor of the Na ⁺ /Ca ²⁺ exchanger (NCX); H89, a protein kinase A (PKA) inhibitor; and KN-93, a Ca ²⁺ /calmodulin-dependent protein kinase II (CaMKII) inhibitor. These results suggest that enhancement of late I _Na in the pulmonary vein cardiomyocytes causes disturbance of the intracellular ion environment through activation of the NCX and Ca ²⁺ -dependent enzymes. Such mechanisms are probably involved in the ectopic electrical activity of the pulmonary vein myocardium.