Sympathetic innervation directs localization of ankyrin g, nav and kcnq1 channels to neuro-cardiac junctions

Abstract

AbstractThe sympathetic nervous system plays a central role in the cardiovascular response to acute stress by increasing heart rate and contractility. Despite the importance of functional connections between sympathetic nerves and cardiac myocytes, very little is known about structural and functional organization of the neuro-cardiac synapses. Earlier, we have demonstrated that specialized signaling domains are organized in cardiac myocytes at sites of contact with sympathetic neurons [Shcherbakova O.G., 2007]. In the present study, we addressed the question if sympathetic innervation may affect localization of the cardiac ion channels. We have found that scaffold protein ankyrin G is localized at the postsynaptic sites in the innervated cardiac myocytes in co-culture with sympathetic neurons. Consistent with roles of ankyrin G in targeting Nav channels to excitable domains in neurons and cardiac myocytes, we have observed an increased density of Nav channels at the neuro-cardiac junctions. We have also found that KCNQ1 channels are enriched at that sites. The increased density of Nav and KCNQ1 channels at the sites of sympathetic innervation is likely to enable a fine-tuning of particular currents by neuronal input.