Diabetes reduces the heart’s capacity and increases the incidence of heart failure dramatically. Decades of research has tested the hypothesis that attenuated contractility in the diabetic heart occurs because the magnitude of rhythmic intracellular calcium spikes (flux), which trigger contraction of force-generating myofilaments. However cardiac drugs that improve intracellular calcium handling are less effective in people with diabetes, and we recently restored contractility in diabetic hearts without changing intracellular calcium, suggesting intracellular calcium regulation is not deficient in the diabetic heart. We now propose to use a new single cell physiology system to test the alternative hypothesis that the calcium sensitivity of the myofilament (e.g. not calcium flux) is reduced in diabetic heart cells. If our hypothesis is supported, it will challenge the well-established theory that intracellular calcium availability underlies diabetic cardiac dysfunction and provide a new target (myofilament calcium sensitivity) for developing therapies.