Cardiac β-adrenergic Signaling

β-adrenergic receptor (β-AR) stimulation by the neurotransmitter norepinephrine (NE) plays a key role in modulation of cardiac function in response to stress or exercise. β1-ARs are coupled to Gαs. Stimulation of the receptor results in Gαs mediated activation of adenylate cyclase (AC) which then catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). Higher cAMP levels lead to PKA activation which regulates a number of Ca+2 cycling proteins like L-type Ca+2 channel, SERCA and (phospholamban) PLN. In the heart, excitation-contraction (EC) coupling is driven by an ion-channel-mediated calcium cycle that produces myofilament contraction and relaxation. Thus, β-AR signaling controls cardiac contractility.