Recently, it has been reported that the protein kinase C (PKC) ␤ isoform plays a critical role in the development of hypertrophy and heart failure. The purpose of the present study was to clarify the mechanism by which activation of PKC ␤ led to depressed cardiac function. Thus, we used a PKC ␤ 2 overexpressing mouse, an animal model of heart failure, to examine mechanical properties and Ca 2 ϩ signals of isolated left ventricular cardiomyocytes. The percentage of shortening, rate of shortening, and rate of relengthening of cardiomyocytes were markedly reduced in PKC ␤ 2 overexpression mice compared to wild-type control mice, although the baseline level and amplitude of Ca 2 ϩ signals were similar. These findings suggested a decreased myofilament responsiveness to Ca 2 ϩ in transgenic hearts. Therefore, the incorporation of