Human 5-HT 4 receptor stimulation in atria of transgenic mice

摘要: In human atrium, serotonin (5-HT) exerts pleiotropic effects, which are thought to be mediated via 5-HT4 receptors. Here, we used transgenic mice (TG) that overexpress the 5-HT4(a) receptor under control of heart-specific α-myosin heavy chain promoter in atria (and ventricles). Contractile studies were performed isolated electrically driven left atrial preparations and spontaneously beating right preparation TG littermate (wild type (WT)). 5-HT increased force contraction phospholamban phosphorylation on serine 16 only from but not WT. contrast, β-adrenoceptor stimulation by isoprenaline with similar pEC50 values a maximum extent both The contractile effects could blocked receptor-specific antagonists GR125487 or GR113808. WT TG, agonist exerted positive chronotropic effect effects. Only WT, attenuated antagonists. Finally, higher incidence arrhythmias was noted compared present data indicate receptors expressed mouse functional. This is first model study this atrium ex vivo vivo.