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Adenylyl cyclase (AC) represents one of the principal molecules in the β-adrenergic receptor signaling pathway, responsible for the conversion of ATP to the second messenger, cAMP. AC types 5 (AC_V) and 6 (AC_VI) are the 2 main isoforms in the heart. Although highly homologous in sequence, these 2 proteins play different roles during the development of heart failure. Caveolin-3 is a scaffolding protein, integrating many intracellular signaling molecules in specialized areas called caveolae. In cardiomyocytes, caveolin is located predominantly along invaginations of the cell membrane known as t-tubules.

We take advantage of AC_V and AC_VI knockout mouse models to test the hypothesis that there is distinct compartmentalization of these isoforms in ventricular myocytes.

We demonstrate that AC_V and AC_VI isoforms exhibit distinct subcellular localization. The AC_VI isoform …