α7 nicotinic receptors play a role in regulation of cardiac hemodynamics

Abstract

The α7 nicotinic receptors (NR) have been confirmed in the heart but their role in cardiac functions has been contradictory. To address these contradictory findings, we analyzed cardiac functions in α7 NR knockout mice (α7−/−) in vivo and ex vivo in isolated hearts. A standard limb leads electrocardiogram was used, and the pressure curves were recorded in vivo, in Arteria carotis and in the left ventricle, or ex vivo, in the left ventricle of the spontaneously beating isolated hearts perfused following Langedorff's method. Experiments were performed under basic conditions, hypercholinergic conditions, and adrenergic stress. The relative expression levels of α and β NR subunits, muscarinic receptors, β1 adrenergic receptors, and acetylcholine life cycle markers were determined using RT‐qPCR. Our results revealed a prolonged QT interval in α7−/− mice. All in vivo hemodynamic parameters were preserved under all studied conditions. The only difference in ex vivo heart rate between genotypes was the loss of bradycardia in prolonged incubation of isoproterenol‐pretreated hearts with high doses of acetylcholine. In contrast, left ventricular systolic pressure was lower under basal conditions and showed a significantly higher increase during adrenergic stimulation. No changes in mRNA expression were observed. In conclusion, α7 NR has no major effect on heart rate, except when stressed hearts are exposed to a prolonged hypercholinergic state, suggesting a role in acetylcholine spillover control. In the absence of extracardiac regulatory mechanisms, left ventricular systolic impairment is revealed.image

Recent advances in cholinergic mechanisms: A preface for the ISCM2022 special issue

“…Given the fundamental identification of the first neurotransmitter receptor and ligand-gated ion channel (Changeux et al, 1970), the recently solved structures of nicotinic receptors and their snake-and plant-produced toxins were elegantly presented by Ryan Hibbs (Rahman et al, 2020(Rahman et al, , 2022. Nicotinic receptors also seem to have direct actions in cardiac tissue, which was covered by Anna Hrabovska using KO mice and published in this issue (Targosova et al, 2023).…”