Fig. 1. Cardiac adrenergic receptors and polymorphisms relevant to β-blocker responsiveness. Shown are the presynaptic α^2A- and α^2CARs, which when activated by epinephrine or norepinephrine, decrease norepinephrine release from the presynaptic nerve terminal. Presynaptic β²AR activation increases norepinephrine release: on the cardiomyocyte, catecholamine-activated β¹AR and β²AR increase inotropy and chronotropy, and can under-signal dampening because of receptor phosphorylation by GRKs (G-protein coupled receptor kinase).