Core of basic research: Deciphers the molecular mechanism by which epinephrine (Epi) and norepinephrine (NE) regulate myocardial contractility, heart rate, and metabolism, a key pathway for cardiovascular regulation under stress. Epi/NE binding to β1 receptors (major subtype) on cardiomyocyte membranes activates Gs proteins, promoting AC to generate cAMP. cAMP activates PKA, which phosphorylates key downstream substrates: ① L-type calcium channels (LTCC) enhance calcium influx and sarcoplasmic reticulum (SR) calcium storage; ② SR calcium release channels (RyR2) promote calcium-induced calcium release (CICR) to enhance myocardial contractility; ③ Troponin I (TnI) reduces myofilament calcium sensitivity to accelerate relaxation; ④ Phospholamban (PLB) relieves its inhibition of SR calcium ATPase (SERCA) to promote calcium reuptake and rapid myocardial relaxation. Additionally, α1 receptor activation regulates the PLC-γ pathway via Gq proteins, participating in myocardial remodeling. Research focuses on the signal transduction specificity of β1 receptors, phosphorylation regulation of PKA substrates, pathway desensitization mechanisms (β-arrestin-mediated receptor internalization), associations between excessive pathway activation and myocardial hypertrophy/heart failure, and therapeutic mechanisms of β-blockers (e.g., metoprolol).
Core key proteins: Epinephrine (Epi), norepinephrine (NE), β1/β2/α1 receptors (adrenergic receptors), Gs/Gq proteins (receptor-coupled proteins), AC (adenylyl cyclase), cAMP, PKA (protein kinase A), L-type calcium channel (LTCC), RyR2 (SR calcium release channel), TnI (troponin I), PLB (phospholamban), SERCA (SR calcium ATPase), β-arrestin (receptor desensitization regulatory protein), MAPK (ERK/JNK/p38, involved in myocardial remodeling), cardiomyocytes.