SPONTANEOUS ACTIVITY IN TRANSGENIC MOUSE HEART - COMPARISON OF PRIMARY ATRIAL TUMOR WITH CULTURED AT-1 ATRIAL MYOCYTES

Introduction: We have generated transgenic animals that heritably deve lop atrial tumors composed of differentiated proliferating cardiomyocy tes. Experiments were initiated to characterize, the electrical proper ties of these cells. Methods and Results: We show that the primary atr ial tumors are composed of discrete foci that exhibit spontaneous auto matic activity. A direct correlation was observed between tumor size a nd firing rate of these foci. In addition to the primary atrial tumors , we examined the properties of cultured cardiomyocytes isolated from a transplantable transgenic tumor lineage (designated AT-1 cells). Cul tured AT-1 cells are also spontaneously automatic. The action potentia l configuration from these preparations is similar to that observed in nontransgenic atrial cardiomyocytes, albeit somewhat more depolarized and of longer duration. As would be expected for cardiomyocytes of at rial origin, the transgenic cardiomyocyte preparations hyperpolarize d uring muscarinic stimulation due to increased K+ conductance mediated by a pe toxin sensitive G-protein. Assessment of pharmacologic blockag e of the ''i(f)'' pacemaker current suggests that the automaticity of both transgenic cardiomyocyte preparations may be of novel origin. In this context, the cultured AT-1 cells showed spontaneous behavior that was dearly of cellular origin; this activity was manifest as transien t bursts of electrical activity followed by periods of electrical quie scence. This bursting pattern is unusual for normal adult cardiomyocyt es, but has been observed in several other cell types. In the primary tumors, automatic behavior may arise from a similar cellular origin or alternatively from a microreentrant phenomena. Conclusion: Primary tu mors and AT-1 cells show essential atrial electrophysiology with impor tant novel features.