Aim: To evaluate the role of the Na+-Ca2+ exchange current in the induction of arrhythmias during Ca2+ waves, we investigated the relationship between Ca2+ waves and delayed afterdepolarizations (DADs) and further investigated the effect of KB-R7943, an Na+-Ca2+ exchange inhibitor, on such relationship in multicellular muscle.
Methods: Force, sarcomere length, membrane potential, and [Ca2+]i dynamics were measured in 32 ventricular trabeculae from rat hearts. After the induction of Ca2+ waves by trains of electrical stimuli (400, 500, or 600 ms intervals) for 7.5 seconds, 23 Ca2+ waves in the absence of KB-R7943 and cilnidipine ([Ca2+]o = 2.3 +/- 0.2 mmol/L), 11 Ca2+ waves in the presence of 10 micromol/L KB-R7943 ([Ca2+]o = 2.5 +/- 0.5 mmol/L), and 8 Ca2+ waves in the presence of 1 micromol/L cilnidipine ([Ca]o = 4.1 +/- 0.3 mmol/L) were measured at a sarcomere length of 2.1 microm (23.9 +/- 0.8 degrees C).
Results: The amplitude of DADs correlated with the velocity (r = 0.90) and the amplitude (r = 0.90) of Ca2+ waves. The amplitude of DADs was significantly decreased to approximately 40% of the initial value by 10 micromol/L KB-R7943.
Conclusions: These results suggest that the velocity and the amplitude of Ca2+ waves determine the formation of DADs principally through the activation of the Na+-Ca2+ exchange current, thereby inducing triggered arrhythmias in multicellular ventricular muscle.