Mechanism of the slow inotropic response of the mouse atrium mediated by the beta2-adrenoreceptor

The abundant beta2-adrenoceptors (AR) expression was revealed in the mouse atrial cardiomyocytes, albeit its function is poorly understood. Recently we revealed the slow developing (for 20-40 min) positive inotropic effect in the mouse atrium which was induced by the specific agonist of the beta2-adrenoceptors (5 mkM fenoterol) and the task of this study involved investigation of the found effect. It was shown that stimulation of beta2-AR is enough for rapid triggering of up-regulation of two signalling pathways that have the opposite influence on the contraction force. On one hand, activation of the adenylate cyclase--protein kinase A cascade occurs leading to increasing of intracellular Ca2+ concentration and amplitude of contraction; on the other hand, activation of the NO-synthase and enhance of NO production occurs which prevents the potentiating of the contraction force. During the first 15-20 minutes, superposition of these activation effects was revealed, which prevented the contraction strength increasing. Then the positive inotropic effects occurred due to the decreasing of NO production. It was shown that L-type Ca-channels and ryanodine receptors were the key targets incorporated in the beta2 adrenoreceptors signalling puzzle.     

25-Hydroxycholesterol as a Signaling Molecule of the Nervous System

Biochemistry (Moscow) - Cholesterol is an essential component of plasma membrane and precursor of biological active compounds, including hydroxycholesterols (HCs). HCs regulate cellular homeostasis...