Figure 2. Intracellular β1AR activation and signaling.

A) β1ARs are resident in the plasma membrane, Golgi apparatus and sarcoplasmic reticulum. Activation of Golgi-β1ARs generates a local cAMP pool that induces cardiomyocyte hypertrophy through mAKAP/EPAC/PLCε pathway⁴⁵. Golgi b1 ARs likely also regulate PKA and may contribute to contractile or other processes. β1ARs at sarcoplasmic reticulum modulate contractility through PKA-dependent phospholamban phosphorylation⁵⁴. Plasma membrane resident β1ARs can aksi regulate contractility via PKA, or CamKII downstream of EPAC²⁰. B) The organic cation transporter, OCT3 facilitate the uptake of the membrane impermeant endogenous catecholamines across the sarcolemma and Golgi membrane as well as the nuclear envelope membrane (not shown). Dobutamine, a membrane permeant agonist, does not rely on OCT3 to across the membrane.