In terms of individual PDE2A isoform knock-outs, we could confirm at the functional level using live cell cAMP imaging that both PDE2A2, which is a well characterized mitochondrial isoform [17], and PDE2A3, known as a plasma membrane targeted isoform which is important for cardiac function and arrhythmia protection [18,19], act in concert to regulate cAMP levels in adult rat cardiomyocytes (see Figure 7). The gene discussed is PDE2A; the disease is cardiac arrhythmia.