Figure 50-46 A and B, Signal systems involved in positive inotropic and lusitropic (enhanced relaxation) effects of β-adrenergic stimulation. When the β-adrenergic agonist interacts with the β-receptor, a series of G protein-mediated changes lead to activation of adenylate cyclase and the formation of cyclic adenosine monophosphate (cAMP). The latter acts via protein kinase A to stimulate metabolism (left) and phosphorylate the calcium channel protein. The result is an enhanced probability of the calcium channel being open, thereby increasing the inward movement of Ca²⁺ ions through the sarcolemma (SL) of the T tubule. These Ca²⁺ ions release more calcium from the sarcoplasmic reticulum (SR) to increase cytosolic calcium and activate troponin C. Calcium ions also increase the rate of breakdown of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate (P_i ). Enhanced myosin ATPase activity explains the increased rate of contraction, with increased activation of troponin C explaining the development of increased peak force. An increased rate of relaxation is explained by the fact that cAMP also activates the protein phospholamban (PL), which is situated on the membrane of the SR and controls the rate of uptake of calcium into the SR. The latter effect explains enhanced relaxation (lusitropic effect). TnI, troponin I. (From Opie LG: Receptors and signal transduction. In Opie LH [ed]: The Heart, Physiology from Cell to Circulation, 4th ed. Philadelphia, Lippincott Raven, 1997, pp 173–207.)