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. 2007 Jul;10(2):99-104.

Beta-adrenergic receptor signaling in cardiac function and heart failure

Aasakiran Madamanchi

Beta-adrenergic receptor signaling in cardiac function and heart failure

Aasakiran Madamanchi. Mcgill J Med. 2007 Jul.
No abstract available

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Figures

Figure 1
Figure 1
Classical GPCR signaling. Agonist binding to the receptor results in the coupling with G-proteins and exchange of G-protein-bound GDP for GTP. The activated G-protein dissociates into Ga and Gbg subunits, both of which independently affect cellular signaling through the activation or inhibition of effectors such as adenylyl cyclase (AC) or phospholipase C-b (PLC-b). Ga subunits are grouped into four subfamilies - GaS, Gai, Gaq and Ga12 - based on their structure and function. The members of stimulatory Gas family couple to AC to cause an increase in intracellular cAMP levels, whereas members of Gai family inhibit AC and decrease cAMP levels. The members of Gaq activate PLC-b, whereas members of Ga12 family activate Rac and Rho. Gβγ dimers activate large number of effectors including ion channels, mitogenactivated protein (MAP) kinases and activate or inhibit AC.
Figure 2
Figure 2
β-AR-mediated cardiomyocyte contractility. Agonist binding stimulates β1-AR and results in coupling with and activation of heterotrimeric Gs, which dissociates into GaS and Giβγ subunits. The GaS activates both adenylyl cyclase (AC), which increases intracellular cAMP levels and L-type calcium channel, which allows Ca2+ to enter into cardiomyocytes. The cAMP activates PKA, which phosphorylates (P) several substrates including phospholamban (PLB), L-type Ca2+ channels, troponin I and the cardiac ryanodine receptor (RyR) resulting in increased cardiac contractility and relaxation. In addition to Gs, β2-AR couples to pertussis toxin-sensitive Gi upon agonist binding. Activated-Gi releases Gai subunit, which inhibits AC and Giβγ and activates phospholipase A2 (cPLA2) leading to reduced cardiac contractility. The β1-AR-induced cAMP suppresses the β2-AR/cPLA2 pathway, via PKA. Asterisks denote activated proteins and indicates inhibition.
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