We conclude that phosphodiesterase inhibition uncovers functional ventricular 5-HT(4) receptors, coupled to a PKA pathway, through which 5-HT enhances contractility, hastens relaxation and can potentially cause arrhythmias.
This supports the hypothesis that the observed alterations in mRNA transcription in AF patients may lead to a decrease in the availability of functional L-type Ca2+-channels and 5-HT4-receptors and/or reduce L-type Ca2+-current amplitude and density, thus, promoting and stabilizing the arrhythmia.
The effect of the 5-HT4 antagonists GR113808A and GR125487D on cocaine-induced cardiac arrhythmia was examined in the rat.Cocaine alone, given i.v. at a rate of 2 mg/kg every 5 min, produced an initial increase in blood pressure followed by a severe drop in pressure and bradycardia.