Segregation of calcium signalling mechanisms in magnocellular neurones and terminals

Abstract

Every cell or neuronal type utilizes its own specific organization of its Ca2+ homeostasis depending on its specific function and its physiological needs. The magnocellular neurones, with their somata situated in the supraoptic and paraventricular nuclei of the hypothalamus and their nerve terminals populating the posterior hypophysis (neural lobe) are a typical and classical example of a neuroendocrine system, and an important experimental model for attempting to understand the characteristics of the neuronal organization of Ca2+ homeostasis. The magnocellular neurones synthesize, in a cell specific manner, two neurohormones: arginine-vasopressin (AVP) and oxytocin (OT), which can be released, in a strict Ca2+-dependent manner, both at the axonal terminals, in the neural lobe, and at the somatodendritic level. The two types of neurones show also distinct type of bioelectrical activity, associated with specific secretory patterns. In these neurones, the Ca2+ homeostatic pathways such as the Na+/Ca2+ exchanger (NCX), the endoplasmic reticulum (ER) Ca2+ pump, the plasmalemmal Ca2+ pump (PMCA) and the mitochondria are acting in a complementary fashion in clearing Ca2+ loads that follow neuronal stimulation. The somatodendritic AVP and OT release closely correlates with intracellular Ca2+ dynamics. More importantly, the ER Ca2+ stores play a major role in Ca2+ homeostatic mechanism in identified OT neurones. The balance between the Ca2+ homeostatic systems that are in the supraoptic neurones differ from those active in the terminals, in which mainly Ca2+ extrusion through the Ca2+ pump in the plasma membrane and uptake by mitochondria are active. In both AVP and OT nerve terminals, no functional ER Ca2+ stores can be evidenced experimentally. We conclude that the physiological significance of the complexity of Ca2+ homeostatic mechanisms in the somatodendritic region of supraoptic neurones and their terminals can be multifaceted, attributable, in major part, to their specialized electrical activity and Ca2+-dependent neurohormone release.