| First Author | Yao X | Year | 2015 |
| Journal | Glia | Volume | 63 |
| Issue | 10 | Pages | 1860-9 |
| PubMed ID | 25944186 | Mgi Jnum | J:223939 |
| Mgi Id | MGI:5660680 | Doi | 10.1002/glia.22853 |
| Citation | Yao X, et al. (2015) Aquaporin-4 regulates the velocity and frequency of cortical spreading depression in mice. Glia 63(10):1860-9 |
| abstractText | The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space (ECS) K(+) concentration ([K(+) ]e ) and volume dynamics following neuronal activation. Here, we investigated how AQP4-mediated changes in [K(+) ]e and ECS volume affect the velocity, frequency, and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild-type (AQP4(+/+) ) and AQP4-deficient (AQP4(-/-) ) mice. In contrast to initial expectations, both the velocity and the frequency of CSD were significantly reduced in AQP4(-/-) mice when compared with AQP4(+/+) mice, by 22% and 32%, respectively. Measurement of [K(+) ]e with K(+) -selective microelectrodes demonstrated an increase to approximately 35 mM during spreading depolarizations in both AQP4(+/+) and AQP4(-/-) mice, but the rates of [K(+) ]e increase (3.5 vs. 1.5 mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4(-/-) mice. ECS volume fraction measured by tetramethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4(+/+) mice, and 0.23 to 0.063 in AQP4(-/-) mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4(-/-) mice was primarily a consequence of the slowed increase in [K(+) ]e during neuronal depolarization. These results demonstrate that AQP4 effects on [K(+) ]e and ECS volume dynamics accelerate CSD propagation. GLIA 2015;63:1860-1869. |
