Induction of cardiac dysfunction in developing and adult zebrafish by chronic isoproterenol stimulation.

Zebrafish is a widely used model to evaluate genetic variants and modifiers that can cause heart muscle diseases. Surprisingly, the β-adrenergic receptor (β-AR) pathway in zebrafish is not well characterized, although abnormal β-AR signaling is a major contributor to human heart failure (HF). Chronic β-AR activation in the attempt to normalize heart function in the failing heart results in a reduction of the β-ARs expression and receptor desensitization, largely mediated through G-protein coupled receptor kinase 2 (GRK2) upregulation.