Selective Sinoatrial Node Optical Mapping and the Mechanism of Sinus Rate Acceleration

抄録

Background: Studies using isolated sinoatrial node (SAN) cells indicate that rhythmic spontaneous sarcoplasmic reticulum calcium release (Ca clock) plays an important role in SAN automaticity. In the intact SAN, cross-contamination of optical signals from the SAN and the right atrium (RA) prevent the definitive testing of Ca clock hypothesis. The aim of this study was to use a novel approach to selectively mapping the intact SAN to examine the Ca clock mechanism. Methods and Results: We simultaneously mapped intracellular Ca (Ca_i) and membrane potential (V_m) in 10 isolated, Langendorff-perfused normal canine RAs. The excitability of the RA was suppressed with high-potassium Tyrode's solution, allowing selective optical mapping of V_m and Ca_i of the SAN. Isoproterenol (ISO, 0.03μmol/L) decreased the cycle length of the sinus beats, and shifted the leading pacemaker site from the middle or inferior SAN to the superior SAN in all RAs. The Ca_i upstroke preceded the V_m in the leading pacemaker site by up to 18±2ms. ISO-induced changes to SAN were inhibited by ryanodine (3μmol/L), but not ZD7288 (3μmol/L), a selective I_f blocker. Conclusions: We conclude that, in the isolated canine RA, a high extracellular potassium concentration can suppress atrial excitability thus leading to SAN-RA conduction block, allowing selective optical mapping of the intact SAN. Acceleration of Ca cycling in the superior SAN underlies the mechanism of sinus tachycardia during sympathetic stimulation.