Abstract 3504: Maintenance of Triggered Arrhythmias by Non-Uniform Excitation-Contraction Coupling in Rat Cardiac Muscle
Non-uniform excitation-contraction coupling (ECC) enhances delayed afterdepolarizations by inducing a Ca2+ surge within the border zone (BZ) between contracting and stretched regions, and initiates triggered arrhythmias. To elucidate the role of non-uniform ECC in the maintenance of triggered arrhythmias, we examined the effect of sarcomere length on cycle lengths of triggered arrhythmias. Force was measured in rat trabeculae with a strain gauge, sarcomere length with a laser diffraction technique, membrane potential with an ultracompliant microelectrode. To produce non-uniform ECC, a restricted region (~300 μm length) of muscle was exposed to a jet of 20 mM 2,3-butanedione monoxime (BDM), causing sarcomere stretch inside the region during twitches. To induce sustained arrhythmias, stimulus trains with cycle lengths ranging from 200 to 500 ms for 7.5 s were added (100 nM isoproterenol, [Ca2+]o = 1.0 mM, 24°C). Triggered arrhythmias were regarded as sustained when they lasted more than 10 s. To modulate myofilament-Ca2+ affinity inside the BDM jet region, muscle length was changed from 2.0 to 2.2 or 1.9 μm during sustained arrhythmias. The longest cycle length of stimulus trains required to induce sustained arrhythmias was 412 ± 28 ms in the presence of the BDM jet (n = 6). In the absence of the BDM jet, however, stimulus trains with cycle lengths of 200, 300, and 400 ms could not induce sustained arrhythmias (n = 6). Lengthening of sarcomere from 2.0 to 2.2 μm during sustained arrhythmias shortened the cycle length by 8 ± 3 % (n = 6, P < 0.01), and shortening of sarcomere from 2.0 to 1.9 μm during sustained arrhythmias lengthened the cycle length by 4 ± 2 % (n = 6, P < 0.01). The maximum rate of force relaxation correlated inversely with the changes in cycle lengths of sustained arrhythmias (n = 14, P < 0.01). 100 μM streptomycin, a stretch-activated channel blocker, did not suppress the changes in the cycle lengths caused by the changes in sarcomere length (n=6). These results suggest that modulation of myofilament-Ca2+ affinity within the BZ can affect cycle lengths of sustained arrhythmias by changing Ca2+ dissociation from myofilaments. Thus, non-uniform ECC plays an important role in the maintenance of triggered arrhythmias.