Mammals defend against large changes in extracellular fluid osmolality by making appropriate changes in salt and water ingestion, and by inducing complementary changes in Na+ and water excretion by the kidney. The former responses are mediated by changes in behaviour; the latter are mediated by changes in hormone release and by autonomic innervation of the kidney.
These osmoregulatory responses are controlled by osmoreceptors — specialized neurons that encode the osmotic set-point in their basal rate of action-potential discharge and that can mediate the effects of hypotonicity or hypertonicity through proportional changes in the rate of action-potential firing.
Osmosensory transduction in osmoreceptor neurons is a mechanical process during which osmotically induced changes in cell volume lead to inverse changes in the probability of opening of nonselective cation channels that might be members of the transient receptor potential vanilloid family of ion channels.
Osmoreceptor neurons are located in a number of areas in the periphery and in the brain. Signals derived from peripheral osmoreceptors reach the brain through the vagus nerve and the spinal cord. Primary cerebral osmoreceptors are located in the organum vasculosum of the lamina terminalis. Signals derived from both sources are integrated in a number of brain areas.
Peripheral osmoreceptors signal ingestion-related information that is used to adjust osmoregulatory responses before ingested salt or water has an impact on systemic osmolality. In contrast to these anticipatory effects of peripheral osmoreceptors, central osmoreceptors relay sustained information concerning the online systemic osmotic status of the animal.
The information that is encoded by osmoreceptors is integrated in various parts of the brain and is ultimately relayed to neurons in the frontal cortex that command specific behaviours and to specific subsets of neuroendocrine and pre-autonomic neurons in the hypothalamus to modulate renal function.
Systemic osmoregulation is a vital process whereby changes in plasma osmolality, detected by osmoreceptors, modulate ingestive behaviour, sympathetic outflow and renal function to stabilize the tonicity and volume of the extracellular fluid. Furthermore, changes in the central processing of osmosensory signals are likely to affect the hydro-mineral balance and other related aspects of homeostasis, including thermoregulation and cardiovascular balance. Surprisingly little is known about how the brain orchestrates these responses. Here, recent advances in our understanding of the molecular, cellular and network mechanisms that mediate the central control of osmotic homeostasis in mammals are reviewed.
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Work in the author's laboratory is supported by operating grants MOP-9939 and MOP-82818 from the Canadian Institutes of Health Research and by a James McGill Research Chair. The Research Institute of the McGill University Health Centre receives support from the Fonds de la Recherche en Santé du Québec.
A quantitative measure of the total solute concentration in a solution expressed in moles per kilogram of solution. Osmolality is not the same as osmolarity, which is the number of moles of total solutes per litre of solution.
Any dissolved substance that contributes to the osmolality of a solution.
- Hypertonic conditions
Conditions in which the ECF contains a higher concentration of membrane-impermeant solutes than is observed at rest in that particular species.
An increase in the flow of urine produced by the kidney.
The excretion of Na+ in urine.
A condition in which a solution has a higher concentration of free Na+ than is normal for the species in question.
- Patch-clamp pipette
A glass pipette with a tip diameter of approximately 1 μm. To make patch-clamp recordings, it is filled with a medium that approximates the composition of the cytoplasm. It is held by a plastic holder that makes a contact between this fluid and a silver electrode attached to an amplifier. A flexible tube connected to the same holder is used to alter the hydrostatic pressure inside the pipette and the cell to which it is connected.
- Organic osmolyte
An organic molecule that is synthesized by a cell to increase the effective osmolality of the intracellular compartment and thus resist the shrinking that would otherwise be caused by extracellular hypertonicity.
A condition in which the plasma has a lower concentration of free Na+ ions than is normal for the species in question.
The posterior pituitary gland, also known as the pars nervosa of the pituitary.
- Dilutional hyponatraemia
A condition in which the plasma becomes hyponatraemic as a result of excessive water intake, as opposed to as a result of sodium loss.
- Hypovolaemic hyponatraemia
A condition in which the plasma becomes hyponatraemic in combination with a significant reduction in total blood volume.
- Superfused explant
A small explant of adult brain tissue that is kept functional by the superfusion of an oxygenated artificial cerebrospinal fluid.
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Bourque, C. Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci 9, 519–531 (2008). https://doi.org/10.1038/nrn2400
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