Involvement of the Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in the Automaticity of the Cardiomyocytes from the Guinea Pig Pulmonary Vein but Not the Sinus Node

Fluorescence imaging analysis was performed in cardiomyocytes from the sinus node, the orthotopic pacemaker, and the pulmonary vein, a potential ectopic pacemaker that may cause atrial fibrillation, focusing on the role of the Na⁺/Ca²⁺ exchanger (NCX). Isolated cardiomyocytes from the guinea pig pulmonary vein and sinus node showing automaticity were loaded with fluorescence probes for analysis. Inhibition of NCX by SEA0400 decreased the Ca²⁺ transient frequency in the pulmonary vein cardiomyocytes but not in the sinus node. The basal intracellular Ca²⁺ concentration, as well as the number of Ca²⁺ sparks in the subsarcolemmal region, was higher in the pulmonary vein cardiomyocytes than in the sinus node. By contrast, the intracellular Na⁺ concentration was not different between the pulmonary vein and sinus node cardiomyocytes. The equilibrium potential for NCX (E_NCX) was estimated to be less negative in the pulmonary vein cardiomyocytes than in the sinus node. In conclusion, the forward mode NCX is involved in spontaneous activity in the pulmonary vein cardiomyocytes but not in the sinus node; this is probably because the Ca²⁺ supply and the driving force for the forward mode NCX are both larger in the pulmonary vein cardiomyocytes than in the sinus node.