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. 2001 May 1;21(9):3045-51.
doi: 10.1523/JNEUROSCI.21-09-03045.2001.

A novel role of vasopressin in the brain: modulation of activity-dependent water flux in the neocortex

H Niermann  1 , M Amiry-Moghaddam, K Holthoff, O W Witte, O P Ottersen
Affiliations

A novel role of vasopressin in the brain: modulation of activity-dependent water flux in the neocortex

H Niermann et al. J Neurosci. .

Abstract

The brain contains an intrinsic vasopressin fiber system the function of which is unknown. It has been demonstrated recently that astrocytes express high levels of a water channel, aquaporin-4 (AQP4). Because vasopressin is known to regulate aquaporin expression and translocation in kidney collecting ducts and thereby control water reabsorption, we hypothesized that vasopressin might serve a similar function in the brain. By recording intrinsic optical signals in an acute cortical slice preparation we showed that evoked neuronal activity generates a radial water flux in the neocortex. The rapid onset and high capacity of this flux suggest that it is mediated through the AQP4-containing astrocytic syncytium that spans the entire thickness of the neocortical mantle. Vasopressin and vasopressin receptor V1a agonists were found to facilitate this flux. V1a antagonists blocked the facilitatory effect of vasopressin and reduced the water flux even in the absence of any exogenous agonist. V2 agonists or antagonists had no effect. These data suggest that vasopressin and V1a receptors play a crucial role in the regulation of brain water and ion homeostasis, most probably by modulating aquaporin-mediated water flux through astrocyte plasma membranes.

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Figures

Fig. 1.
Fig. 1.
Effect of vasopressin on darkening of the intrinsic optical signal (black wave) corresponding to extracellular space widening. The top panelsshow the IOSs and field potentials evoked by afferent stimulation in the neocortical slice. Slices were electrically stimulated every 10 min with stimulus trains lasting 2 sec. Extracellular field potentials shown were recorded in layer IV and depict the response to the first stimulus within the stimulus train. IOSs were captured 6 sec after stimulation was started. The stimulation electrode in layer VI is shown schematically in this Figure.a, IOS and field potentials under control conditions.b, Increased IOS but similar field potentials after 30 min superfusion with AVP. c, Widening of extracellular space: correlation between TMA+ activity (left panel) and IOS (right panel). d, Statistics of field potentials under control conditions, in the presence ofAVP and in the presence of aV1-antagonist. FP, Field potentials. The differences do not reach statistical significance. Scale bar, 200 μm.
Fig. 2.
Fig. 2.
Changes of potassium ion activity accompanying black waves. IOS and measurements of extracellular potassium ion activity in layers I and IV of the cortex under control conditions (a) and after 30 min superfusion with AVP (b). Slices were electrically stimulated every 10 min with stimulus trains lasting 2 sec. The site where the potassium activity was recorded is indicated by schematic electrodes. Scale bar, 200 μm.
Fig. 3.
Fig. 3.
Pharmacological influences on the size of the black wave. Slices were electrically stimulated every 10 min with stimulus trains lasting 2 sec. a, Typical experiment with application of AVP. After three control stimulations the slice was superfused with AVP, which caused an increase of the black wave. b, Statistics of effects of AVP, the V1-agonist [(Phe2, Ile3, Orn8)]-vasopressin [(Phe2, Orn8)-vasotocin], the V2 agonist (deamino-Cys1,d-Arg8)-vasopressin, the V1-antagonist Phenylac1, d-Tyr(Me)2, Arg6,8, Lys-NH29)-vasopressin, and the V2-antagonist [d(CH2)51,d-Ile4, Arg8, Ala-NH29]-vasopressin on the maximal extension of the black wave. Signal sizes were determined after 40 min of drug application. V2 agonists or V2 antagonists did not affect the size of the black wave. The difference between values for AVP and V1 agonist is not statistically significant (p > 0.05), but both values (and the value for the V1 antagonist) differ from control level (dashed line) and all other observations (p< 0.05). In this and the following Figures the signal size was expressed in arbitrary areal units as measured on-screen.
Fig. 4.
Fig. 4.
Changes of IOS sizes after superfusion with thapsigargin. Slices were electrically stimulated every 10 min with stimulus trains lasting 2 sec. a, Thapsigargin decreased the amplitude of the black wave. Three control stimulations were followed by superfusion with thapsigargin for 60 min. b, In the presence of thapsigargin, AVP did not restore or enhance the black wave. Comparison between thapsigargin (60 min after onset of superfusion) and thapsigargin for 30 min followed by thapsigargin plus AVP for 30 min. There was no significant difference (p > 0.05); however, both values differed from control level (dashed line) atp < 0.05. c, Absence of rundown in a typical control experiment with electrical stimulation every 10 min for 90 min. d, Effects of different concentrations of bisindolylmaleimide I (BIS I) together with AVP (500 nm) on size of the black wave. Signal sizes were determined after 60 min of application. There was no significant difference between the two concentrations (p> 0.05); however, both values differed from control level (dashed line) at p < 0.05.
Fig. 5.
Fig. 5.
a, b, Immunofluorescence labeling of AQP4 in a cortical slice treated with vasopressin. a, Strong AQP4 immunolabeling of the glia limitans (double arrows) facing the unlabeled pia, and of glial end feet surrounding the blood vessels (short arrows). p, Pia. b, Higher magnification showing an unlabeled pial vessel (arrow). Scale bar, 20 μm. c, d, Immunogold labeling of AQP4. c, AQP4 labeling of glial end feet surrounding a collapsed vessel in a cortical slice treated with vasopressin. d, Electron micrograph showing AQP4 labeling of glia limitans facing a pial vessel in rat parietal cortex.V, Vessel lumen; B, basal lamina;G, glial process. Scale bar, 0.3 μm.
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