Spontaneous Activity in Transgenic Mouse Heart:

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Abstract
Spontaneous Activity in Transgenic Mouse Heart and AT‐1 Myocytes. Introduction: We have generated transgenic animals that heritably develop atrial tumors composed of difTerentiated proliferating cardiomyocytes. Experiments were initiated to characterize (he electrical properties of these cells. Methods and Results: We show that the primary atrial tumors are composed of discrete foci that exhibit spontaneous automatic activity. A direct correlation was observed between tumor size and firing rate of these foci. In addition to the primary atrial tumors, we examined the propertie.s of cultured cardiomyocytes isolated from a transplantable transgenic tumor lineage (designated AT‐1 cells). Cultured AT‐1 cells arc al.so spontaneously automatic. The action potential eontiguration from these preparations is similar to that observed in nontransgenic atrial cardiomyocytes, albeit somewbat more depolarized and of longer duration. As would be expected for cardiomyocytes of atrial origin, the transgenic cardiornyocyte preparations hyperpolarize during muscarinic stimulation due to increased K+ conductance mediated by a pertussis toxin sensitive G‐protein. Assessment of pbarmacologic blockage of the “if” pacemaker current suggests that the automaticity of both transgenic cardiomyocyte preparations may be of novel origin. In this context, the cultured AT‐1 cells sbowed spontaneous bebavior that was clearly of cellular origin; this activity was manifest as transient bursts of electrical activity followed by periods of electrical quiescence. this bursting pattern is unusual for normal adult cardiomyocytes, 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 tumors and AT‐1 cells sbow essential atrial Electrophysiology with important novel features.