A Novel Gating Mechanism of Aquaporin-4 Water Channel Mediated by Blast Shockwaves for Brain Edema

Abstract

As the principal water channel in the brain, aquaporin-4 (AQP4) plays a vital role in brain edema, but its role in blast brain edema is unclear. On the basis of molecular simulations, we reveal the atomically detailed picture of AQP4 in response to blast shockwaves. The results show that the shockwave alone closes the AQP4 channel; however, shock-induced bubble collapse opens it. The jet from bubble collapse forcefully increases the distance between helices and the tilt angles of six helices relative to the membrane vertical direction in a very short time. The average channel size increases about 2.6 times, and the water flux rate is nearly 20 times higher than for normal states. It is responsible for abnormal water transport and a potential cause of acute blast brain edema. Additionally, the open AQP4 channel quickly returns to its normal state, which is in turn helpful for edema absorption. Thus, a novel gating mechanism for AQP4 related to the secondary structure change has been provided, which is different from the previous residue-mediated gating mechanism.