Aquaporin‐4 regulates the velocity and frequency of cortical spreading depression in mice. Issue 10 (6th May 2015)

• Record Type: Journal Article
• Authors: Yao, Xiaoming; Smith, Alex J.; Jin, Byung‐Ju; Zador, Zsolt; Manley, Geoffrey T.; Verkman, A. S.
• Is Part Of: Glia. Volume 63:Issue 10(2015:Oct.)
• Page Start: 1860
• Page End: 1869
• Publication Date: 2015-05-06
• Subjects: Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.22853
• Languages: English
• ISSNs: 0894-1491

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The astrocyte water channel aquaporin‐4 (AQP4) regulates extracellular space (ECS) K<sup>+</sup> concentration ([K<sup>+</sup>]<sub>e</sub>) and volume dynamics following neuronal activation. Here, we investigated how AQP4‐mediated changes in [K<sup>+</sup>]<sub>e</sub> and ECS volume affect the velocity, frequency, and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild‐type (AQP4<sup>+/+</sup>) and AQP4‐deficient (AQP4<sup>−/−</sup>) mice. In contrast to initial expectations, both the velocity and the frequency of CSD were significantly reduced in AQP4<sup>−/−</sup> mice when compared with AQP4<sup>+/+</sup> mice, by 22% and 32%, respectively. Measurement of [K<sup>+</sup>]<sub>e</sub> with K<sup>+</sup>‐selective microelectrodes demonstrated an increase to ∼35 mM during spreading depolarizations in both AQP4<sup>+/+</sup> and AQP4<sup>−/−</sup> mice, but the rates of [K<sup>+</sup>]<sub>e</sub> increase (3.5 vs. 1.5 mM/s) and reuptake (<italic>t</italic><sub>1/2</sub> 33 vs. 61 s) were significantly reduced in AQP4<sup>−/−</sup> mice. ECS volume fraction measured by tetramethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4<sup>+/+</sup> mice, and 0.23 to 0.063 in AQP4<sup>−/−</sup> mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4<sup>−/−</sup> mice was primarily a consequence of the slowed increase in [K<sup>+</sup>]<sub>e</sub> during neuronal depolarization. These results demonstrate that AQP4 effects on [K<sup>+</sup>]<sub>e</sub> and ECS volume dynamics accelerate CSD propagation. GLIA 2015;63:1860–1869</p> </abstract>