Abstract 1085: Ectopic Activity Arising at Borderzones Between Myofibroblasts and Cardiomyocytes
Infarct healing involves the local appearance of a large number of myofibroblasts which play a central role in scar formation. Given that myofibroblasts can establish heterocellular gap junctional communication with cardiomyocytes, we investigated whether electrotonic crosstalk between the two cell types might turn the borderzone into a source of ectopic activity. Experiments were performed with patterned growth strands of cultured ventricular cardiomyocytes (600 μm wide, 4.25 mm long). A subset of strands was uniformly coated with myofibroblasts of cardiac origin. Electrical activity was assessed using voltage sensitive dyes and emerging patterns of spontaneous electrical activity were recorded for a duration of 8 s with a fast optical recording system. All experiments were carried out with 3– 4 day old cultures at 36°C. Control preparations exhibiting minimal contamination by endogenous myofibroblasts were invariably quiescent during the entire recording period (n=109). In contrast, when coated uniformly with myofibroblasts, 262 out of 290 preparations (90.3%) showed regular spontaneous activity. As expected based on source-to-load considerations, activations originated preferentially at the ends of the strands (88.6%) and were equally distributed between both ends (43.9% vs. 44.7%). When one end of the strands was extended by an area of pure myofibroblasts in order to simulate the borderzone of a healing infarct, this particular region displayed an increased likelihood of giving rise to spontaneous activity (+ 68%, n=325) as compared to the opposite end. The observation that the sarcolemmal KATP channel opener P-1075 (10 μmol/L) suppressed ectopic activity suggests that partial depolarization of cardiomyocytes caused by the less polarized myofibroblasts was involved in the initiation of spontaneous activity. These findings demonstrate that regions of intimate contact between myofibroblasts and cardiomyocytes can be the source of depolarization-induced abnormal automaticity. To which extent this mechanism may contribute to ectopic activity arising in the borderzone of healing infarcts remains to be shown using appropriate in-vivo models.