Integration of sodium and osmosensory signals in vasopressin neurons

doi:10.1016/S0166-2236(02)02142-2

Trends in Neurosciences

Volume 25, Issue 4, 1 April 2002, Pages 199-205

https://doi.org/10.1016/S0166-2236(02)02142-2 Get rights and content

Abstract

Vasopressin (antidiuretic hormone) release has been thought to be controlled by interacting osmoreceptors and Na⁺-detectors for >20 years. Only recently, however, have molecular and cellular advances revealed how changes in the external concentration of Na⁺ and osmolality are detected during acute and chronic osmotic perturbations. In rat vasopressin-containing neurons, local osmosensitivity is conferred by intrinsic stretch-inactivated cation channels and by taurine release from surrounding glia. Na⁺ detection is accomplished by acute regulation of the permeability of stretch-inactivated channels and by changes in Na⁺ channel gene expression. These features provide a first glimpse of the integrative processes at work in a central osmoregulatory reflex.

Section snippets

CSF [Na⁺] and osmotic pressure are detected in concert

As a group, osmoregulatory responses are believed to be controlled primarily by osmoreceptors – specialized neurons capable of transducing osmotic perturbations into electrical signals 2., 5., 6., 8.. However, in several species, including rats 9., 10. and possibly humans [11], such responses are also regulated by central Na⁺ detectors. For example, both thirst and vasopressin release can be evoked by experimentally induced increases in cerebrospinal fluid (CSF) [Na⁺] in the absence of changes

Magnocellular neurosecretory cells as osmoregulatory neurons

Although the identification of osmoreceptors, Na⁺-detectors and integrative osmoregulatory neurons remains incomplete, such osmoregulatory neurons are now known to be located in the brainstem and in forebrain nuclei adjacent to the anterior wall of the third ventricle (i.e. the lamina terminalis) 2., 4., 7., 17., 18., 19.. Interestingly, the magnocellular neurosecretory cells (MNCs) responsible for the release of oxytocin and vasopressin are themselves sensitive to changes in extracellular [Na⁺

Hormone secretion is controlled by changes in electrical activity

The axon terminals of MNCs cannot fire repetitively in response to sustained depolarization but can be excited at high frequencies by repetitive axon stimulation [26]. Control of vasopressin secretion is therefore achieved primarily through a regulation of the rate at which action potentials are discharged by MNC somata 27., 28.. The osmotic control of MNCs results from an interplay between intrinsic properties, paracrine actions of surrounding glia, and the influence of extrinsic synaptic

Mechanisms of osmoreception in MNCs

Previous in vitro experiments have shown that, in response to acute local osmotic perturbations, rat MNCs display proportional changes in membrane potential that have a significant impact on excitability 30., 35. (Fig. 3b). More recent studies have indicated that the responses of MNCs in situ could reflect the involvement of two distinct processes: an intrinsically generated osmosensory response and a paracrine effect involving neighbouring astrocytes (Fig. 3).

Mechanisms of Na⁺ detection in MNCs

Mechanisms of sufficient sensitivity to allow detection of low millimolar changes in CSF [Na⁺] have been described only recently. In particular, hypothalamic MNCs use a combination of mechanisms to monitor acute and long-term changes in external [Na⁺].

Control of reflex gain during acute perturbation

The findings reviewed above indicate that MNCs are endowed with mechanisms to allow local detection of changes in either extracellular [Na⁺] or osmolality. However, as revealed by McKinley and colleagues [13], concerted changes in these parameters in vivo produce synergistic effects, whereas opposite changes attenuate the responses. These results imply that the slope of the relationship (i.e. ‘gain’) between osmotic pressure and vasopressin release varies as a function of CSF

[Na⁺], and that the

Effects of chronic osmotic stimuli on cell size

Previous studies in vivo have shown that osmoregulatory responses evoked during chronic (e.g. 2–10 days) osmotic perturbation do not display significant adaptation, suggesting that sensory and signalling mechanisms do not fade in the face of prolonged activation 24., 45., 46.. Interestingly, MNCs displayed an increase in cell size during chronic hyperosmolality [47] and a decrease in size during chronic hypoosmolality [48]. These effects are opposite to those occurring during acute (e.g. 1–2 h)

Concluding remarks

Although vasopressin secretion depends on synaptic inputs originating from other osmoregulatory neurons, MNCs themselves currently provide a comprehensive model for signal detection and integration at the cellular level. Hypoosmotic perturbations provoke taurine release from local glia, and by activating glycine receptors on MNCs this contributes to inhibition of firing. Stretch-inactivated cation channels on MNCs transduce acute osmotically evoked changes in cell volume into changes in

Acknowledgements

We thank S.G. Waxman for supplying the panels used in Fig. 5. This work was supported by a Bourse Lavoisier (Ministère des Affaires Étrangères, France) and a CEROC Travel Award (Auvergne, France) to Daniel Voisin, and by MRC Senior Scientist and CIHR operating grants to Charles Bourque.

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However, the central mechanisms by which excess sodium can increase blood pressure (BP) remain poorly defined. Previous work has shown that a rise in plasma sodium can excite hypothalamic magnocellular neurosecretory cells (MNCs) that release the antidiuretic and vasoconstrictor hormone vasopressin (VP) (Bourque, 2008; Voisin and Bourque, 2002). Although VP can enhance BP when infused systemically (Fujiwara et al., 2012), increases in BP normally activate arterial baroreceptors (BR) that inhibit VP MNCs via GABAA receptors (GABAAR) (Cunningham et al., 2002; Renaud et al., 1988).
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Dysfunctions of AQPs are involved in disorders associated with disturbed water homeostasis. Hyponatremia with increased AQP levels can be caused by diseases with low effective circulating blood volume, such as congestive heart failure, or osmoregulation disorders such as the syndrome of inappropriate secretion of antidiuretic hormone. Treatment consists of fluid restriction, demeclocycline and vasopressin type-2 receptor antagonists. Decreased AQP levels can lead to diabetes insipidus (DI), characterized by polyuria and polydipsia. In central DI, vasopressin production is impaired, while in gestational DI, levels of the vasopressin-degrading enzyme vasopressinase are abnormally increased. Treatment consists of the vasopressin analogue dDAVP. Nephrogenic DI is caused by the inability of the kidney to respond to vasopressin and can be congenital, but is most commonly acquired, usually due to lithium therapy. Treatment consists of sufficient fluid supply, low-solute diet and diuretics.
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Trends in Neurosciences

ReviewIntegration of sodium and osmosensory signals in vasopressin neurons

Abstract

Section snippets

CSF [Na+] and osmotic pressure are detected in concert

Magnocellular neurosecretory cells as osmoregulatory neurons

Hormone secretion is controlled by changes in electrical activity

Mechanisms of osmoreception in MNCs

Mechanisms of Na+ detection in MNCs

Control of reflex gain during acute perturbation

Effects of chronic osmotic stimuli on cell size

Concluding remarks

Acknowledgements

Front. Neuroendocrinol.

Front. Neuroendocrinol.

Brain Res.

Kidney Int.

Prog. Neurobiol.

Brain Res.

Neuroscience

Neuroscience

Trends Neurosci.

Prog. Neurobiol.

Trends Neurosci.

Neuron

Neuron

Physiol. Behav.

Neurosci. Lett.

Trends Neurosci.

Hypothalamic integration of body fluid regulation

Proc. Natl. Acad. Sci. U. S. A.

Water intake and body fluids

Osmoreceptors in the central nervous system

Annu. Rev. Physiol.

The antidiuretic hormone and the factors which determine its release

Proc. R. Soc. London Ser. B

Osmoregulation of vasopressin neurons: a synergy of intrinsic and synaptic processes

Prog. Brain Res.

Effect of variation of the composition of CSF in the rat upon drinking of water and hypertonic NaCl solutions

Behav. Neurosci.

Dependence of basic secretion of antidiuretic hormone on cerebrospinal fluid [Na?]

Acta Physiol. Scand.

Cerebrospinal fluid composition and homeostatic responses to dehydration

Thirst – and brain control of water balance

Am. Sci.

Cerebral osmoregulation of renal sodium excretion – a response analogous to thirst and vasopressin release

Can. J. Physiol. Pharmacol.

Influence of mannitol-induced reduction in CSF Na on nervous and endocrine mechanisms involved in the control of fluid balance

Acta Physiol. Scand.

Review
Integration of sodium and osmosensory signals in vasopressin neurons

CSF [Na⁺] and osmotic pressure are detected in concert

Mechanisms of Na⁺ detection in MNCs