A Novel Role of Vasopressin in the Brain: Modulation of Activity-Dependent Water Flux in the Neocortex

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.

Loss of perivascular aquaporin 4 may underlie deficient water and K + homeostasis in the human epileptogenic hippocampus

“…This and other studies (7,8) suggest that buffering of K ϩ by means of inwardly rectifying K ϩ channels on astrocytes depends on a parallel flux of water through the plasma membrane of these cells. Under conditions of high neuronal activity, K ϩ and water are taken up by the astrocyte membrane facing the neuropil and siphoned into blood or cerebrospinal fluid through the endfoot membrane (9).…”

Differential Assembly of Inwardly Rectifying K+ Channel Subunits, Kir4.1 and Kir5.1, in Brain Astrocytes

“…The expression of AQP4 in the brain is restricted to astrocyte membranes facing blood vessels or synaptic terminals (13,38 B, the Kir4.1 carboxyl terminus is crucial for syntrophin interaction. GFP-tagged Kir4.1 lacking the last three amino acid residues at the carboxyl-terminal end (GFP-Kir4.1⌬C3) no longer bound to the ␣ or ␤ 1 -syntrophin GST-fusion proteins described in panel Aa (anti-GFP, third and We compared immunolabeling for either Kir4.1 or Kir5.1 with a specific antibody for AQP4 (Fig.…”

Cell swelling and ion redistribution assessed with intrinsic optical signals

“…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 (Niermann et al 2001). …”