Figure 5
A proposed mechanism of takotsubo syndrome (TTS). (a) β-adrenoceptors (ARs) signaling including G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2 under physiological catecholamine concentrations in cardiomyocyte, which mirrors the state in the normal control group. (b) β-ARs signaling under supraphysiological catecholamine concentrations in cardiomyocyte. GRK2 and β-arrestin2 are overexpressed and subsequently phosphorylation of cyclic-AMP response element binding protein (CREB) is decreased by the inactivation of protein kinase A (PKA) signaling. The reactive oxygen species (ROS) is also produced. GRK2 and β-arrestin2 translocate to the cell membrane, where they are thought to trigger receptor internalization, G-protein uncoupling in β1- and β2-ARs, and Gα protein switching from stimulatory Gαs to inhibitory Gαi in β2-AR. These protective reactions of β-ARs against catecholamine excess and ROS production are associated with some of the mechanisms of developing left ventricular hypokinesis in the TTS heart. AC: adenylyl cyclase, cAMP: cyclic adenosine monophosphate, ATP: adenosine triphosphate.
