GRK2 and heart failure: Our work demonstrates that the dynamics of only the cellular concentrations of cAMP and non-desensitized β1-AR can capture how two of the effects of early heart failure, alteration of the resting levels of adrenergic agonists and upregulation of GRK2, jointly act to change the maximal transient cAMP concentration and the longer-term overall responsiveness of the cell to sympathetic stimulation.