Sympathetic innervation directs Ankyrin G, voltage-gated Nav and KCNQ1 channels to the neuro-cardiac junctions

Abstract

The 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 the structural and functional organization of the neuro-cardiac synapses. Earlier, we demonstrated that specialized signaling domains are organized in cardiac myocytes at sites of contact with sympathetic neurons2. In the present study, we addressed the question if sympathetic innervation may affect localization of the cardiac ion channels. We have found that ankyrin G, scaffold protein involved in targeting ion channels and transporters, is localized at the postsynaptic sites in the cardiac myocytes innervated by sympathetic neurons. Consistent with the roles of ankyrin G in targeting Nav channels to specific domains in neurons and cardiac myocytes, we have observed an increased density of Nav channels at the neuro-cardiac junctions in co-cultures of cardiac myocytes and sympathetic neurons. 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 play a role in regulation of the cardiac excitability by sympathetic nervous system.