Abnormal release of Ca2+ from sarcoplasmic reticulum (SR) via the cardiac ryanodine receptor (RyR2) may contribute to contractile dysfunction in heart failure (HF). We previously demonstrated that RyR2 macromol ecular complexes from HF rat were significantly more depleted of FK506 binding protein (FKBP12.6). Here we assess ed expression of key Ca2+ handling proteins and measured SR Ca2+ content in control and HF rat myocytes. Direct measurements of SR Ca2+ content in permeabilized cardiac myocytes demonstrated that SR luminal [Ca2+] is markedly lowered in HF (HF: Δ F / F 0 = 26.4±1.8, n =12; control: Δ F / F 0 = 49.2±2.9, n =10; P <0.01). Furthermore, we demonstrated that the expression of RyR2 associated proteins (including calmodulin, sorcin, calsequestrin, protein phosphatase 1, protein phosphatase 2A), Ca2+ ATPase (SERCA2a), PLB phosphorylation at Ser16 (PLB-S16), PLB phosphorylation at Thr17 (PLB-T17), L-type Ca 2+ channel (Cav1.2) and Na+-Ca 2+ exchanger (NCX) were significantl y reduced in rat HF. Our results suggest that systolic SR reduced Ca2+ release and diastolic SR Ca2+ leak (due to defective protein-protein interaction between RyR2 and its associated proteins) along with reduced SR Ca2+ uptake (due to down-regulation of SERCA2a, PLB-S16 and PLB- T17), abnormal Ca2+ extrusion (due to down-regulation of NCX) and defective Ca2+-induced Ca2+ release (due to down-regulation of Cav1.2) could co ntribute to HF., S.-T. Hu., and Obsahuje bibliografii a bibliografické odkazy
Monoaminergic neurotransmitter 5-hydroxytryptamine (5-HT), also known as serotonin, plays im portant roles in modulating the function of the olfactory system. However, thus far, the knowledge about 5-HT and its receptors in olfactory receptor neurons (ORNs) and their physiological role have not been fully characterized. In the present study, reverse transcription- polymerase chain reaction (RT-PCR) analysis revealed the presence of 5-HT 1A and 5-HT 1B receptor subtypes in mouse olfactory epithelium at the mRNA level. With subtype selective antibodies and standard immunohistochemical techniques, both receptor subtypes were found to be positively labeled. To further elucidate the molecular mechanisms of 5-HT act on the peripheral olfactory transduction, the whole-cell patch clamp techniques were used on freshly isolated ORNs. We found that 5-HT decreased the magnitude of outward K + current in a dose- dependent manner and these inhi bitory effects were markedly attenuated by the 5-HT 1A receptor blocker WAY-100635 and the 5-HT 1B receptor antagonist GR55562. These data suggested that 5-HT may play a role in the modu lation of peripheral olfactory signals by regulating outward potassium currents, both 5-HT 1A and 5-HT 1B receptors were involved in this regulation., S. Gao, ... [et al.]., and Obsahuje seznam literatury