Enhanced Late INa 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 Ca²⁺ concentrations, increases in the number of Ca²⁺ sparks and Ca²⁺ waves, and the generation of repetitive Ca²⁺ transients. These phenomena were inhibited by eleclazine, a blocker of the late I_Na; SEA0400, an inhibitor of the Na⁺/Ca²⁺ exchanger (NCX); H89, a protein kinase A (PKA) inhibitor; and KN-93, a Ca²⁺/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 Ca²⁺-dependent enzymes. Such mechanisms are probably involved in the ectopic electrical activity of the pulmonary vein myocardium.