Calcium dynamics and the mechanisms of atrioventricular junctional rhythm.

OBJECTIVES The purpose of this study was to test the hypothesis that rhythmic spontaneous sarcoplasmic reticulum calcium (Ca) release (the "Ca clock") plays an important role in atrioventricular junction (AVJ) automaticity. BACKGROUND The AVJ is a primary backup pacemaker to the sinoatrial node. The mechanisms of acceleration of AVJ intrinsic rate during sympathetic stimulation are unclear. METHODS We simultaneously mapped transmembrane potential and intracellular Ca in Langendorff-perfused canine AVJ preparations that did not contain sinoatrial node (n = 10). RESULTS Baseline AVJ rate was 37.5 +/- 4.0 beats/min. The wavefront from leading pacemaker site propagated first through the slow pathway, then the fast pathway and atria. There was no late diastolic Ca elevation (LDCAE) at baseline. Isoproterenol up to 3 micromol/l increased heart rate to 100 +/- 6.8 beats/min, concomitant with the appearance of LDCAE that preceded the phase 0 of action potential by 97.3 +/- 35.2 ms and preceded the onset of late diastolic depolarization by 23.5 +/- 3.5 ms. Caffeine also produced LDCAE and AVJ acceleration. The maximal slope of LDCAE and diastolic depolarization always colocalized with the leading pacemaker sites. Ryanodine markedly slowed the rate of spontaneous AVJ rhythm. Isoproterenol did not induce LDCAE in the presence of ryanodine. The I(f) blocker ZD 7288 did not prevent LDCAE or AVJ acceleration induced by isoproterenol (n = 2). CONCLUSIONS Isoproterenol and caffeine induced LDCAE and accelerated intrinsic AVJ rhythm. Consistent colocalization of the maximum LDCAE and the leading pacemaker sites indicates that the Ca clock is important to the intrinsic AVJ rate acceleration during sympathetic stimulation.

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