Mechanisms of intrinsic osmolality and sodium detection by magnocellular neurosecretory neurons

Abstract

The maintenance of extracellular fluid (ECF) osmolality and sodium concentration ([Na+]o) near optimal “set point” values sustains physiological functions and prevents pathological states such as hypo- and hypernatremia. The peptide hormones vasopressin (antidiuretic hormone) and oxytocin (a natriuretic hormone in rats) play key roles in this process. These hormones are synthesized by hypothalamic magnocellular neurosecretory cells (MNCs) that project to the neurohypophysis and are released into the systemic circulation in response to rises in ECF osmolality or [Na+]o. These homeostatic responses are highly sensitive. For example, vasopressin release is elicited by an increase in ECF osmolality as small as ≥1%. The osmotic and sodium-dependent control of vasopressin and oxytocin release at the neurohypophysis is directly regulated by the electrical activity of MNCs. This regulation involves an array of mechanisms that include synaptic inputs from the brain and periphery, the effects of chemicals released by glial cells, and intrinsic sensory properties of MNCs. These overlapping mechanisms may offer an important degree of redundancy for the homeostatic control of vasopressin and oxytocin release and contribute to the high sensitivity of these responses. Recent work has shown that the intrinsic sodium sensitivity and osmosensitivity of MNCs play an important role in the control of these neurons in vivo. This review provides an update of our current understanding of the molecular and cellular mechanisms that contribute to the cell-autonomous sensory properties of MNCs.