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

Wei, Tong; Zhou, Mi; Gu, Lingzhi; Yang, Hong; Zhou, Yang; Li, Ming

doi:10.1021/acs.jpclett.2c00321

Cited by 9 publications

(4 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, gating mechanisms of AQP4 should also be considered, rather than mere redistribution. Indeed, it has been previously shown that AQP4 gating is dependent on specific conditions (Bernardi et al, 2018 ; Wei et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms Underlying Aquaporin-4 Subcellular Mislocalization in Epilepsy

Szu

Binder

2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Epilepsy is a chronic brain disorder characterized by unprovoked seizures. Mechanisms underlying seizure activity have been intensely investigated. Alterations in astrocytic channels and transporters have shown to be a critical player in seizure generation and epileptogenesis. One key protein involved in such processes is the astrocyte water channel aquaporin-4 (AQP4). Studies have revealed that perivascular AQP4 redistributes away from astrocyte endfeet and toward the neuropil in both clinical and preclinical studies. This subcellular mislocalization significantly impacts neuronal hyperexcitability and understanding how AQP4 becomes dysregulated in epilepsy is beginning to emerge. In this review, we evaluate the role of AQP4 dysregulation and mislocalization in epilepsy.

show abstract

Section: Discussionmentioning

confidence: 99%

Mechanisms Underlying Aquaporin-4 Subcellular Mislocalization in Epilepsy

Szu

Binder

2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Thus, we used the same level of stretch speed in our simulations. In previous work, we revealed that the AQP4 channel was activated by shockwaves on the nanosecond scale. Additionally, shockwaves through the heterogeneous brain composition can give rise to shear forces between cells, resulting in high-speed membrane stretching (∼nanosecond level) .…”

mentioning

confidence: 95%

Extreme Membrane Tensile Loads Induce Half-Activation of the Thermosensitive TRPV1 Channel

Zhou

Wei

et al. 2022

J. Phys. Chem. Lett.

Self Cite

View full text Add to dashboard Cite

Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels convert a wide range of physical and chemical stimuli into channel opening is essential to understanding their normal function. Here, half-activation of thermosensitive TRPV1 channel under extreme membrane stretching from blast loads was provided by molecular dynamics simulations. The results show that such extreme membrane stretch loading will only lead to half-activation of the TRPV1 channel: that is, the upper gate is open for high-speed stretching (>15m/s), but the lower gate is still closed. The corresponding activation threshold also depends on both the tensile speed and the area strain. This means that the direct mechanical gating of TRP channels in one step is unlikely to occur.

show abstract

“…Molecular dynamics (MD) simulations have developed into a powerful tool for providing detailed molecular pictures involved in biological processes, − based on the underlying models. Anatomically, the BBB is composed of endothelial cells, tight junctions (TJs) between endothelial cells, basement membrane, pericyte, and astrocyte end feet.…”

Section: Introductionmentioning

confidence: 99%

How Shockwaves Open Tight Junctions of Blood–Brain Barrier: Comparison of Three Biomechanical Effects

Wei

Zhou

et al. 2022

J. Phys. Chem. B

Self Cite

View full text Add to dashboard Cite

Revealing how blast shockwaves open the tight junction of the blood–brain barrier (BBB) is very important for understanding blast-induced traumatic brain injury (bTBI) and shockwave-assisted drug delivery; however, the underlying mechanism remains unresolved. Here, we used multiscale molecular dynamics simulations to reveal the disruption mechanism of claudin-5 protein in a relatively complex BBB model by comparing three typical effects from blast loads. The results showed that the opening of claudin-5 did not result from the direct compressive loading of the single shockwave but from indirect cavitation and stretching effects induced by shockwaves. Importantly, stretch-mediated mechanical opening from the asymmetric distribution of overpressure in temporal and spatial dimensions is a novel damage mode. In detail, the nanojet from the cavitation pushed away two adjacent endothelial cell membranes and the embedded claudin-5 was rapidly stretched. Even α-helix showed a drastic conformational breakdown and its content was only 15.9%. Structural changes of this magnitude are difficult to repair in a short time, which may be related to chronic BBB dysfunction and persistent neurological deficits. This is a more common injury, since the tensile response of membranes to blast loads is relatively common. Taken together, we provided a biomechanical underpinning for acute disruption of tight junction proteins in BBB from exposure to blast shockwaves, and this may be helpful as a therapeutic strategy for bTBI.

show abstract

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

Cited by 9 publications

References 45 publications

Mechanisms Underlying Aquaporin-4 Subcellular Mislocalization in Epilepsy

Mechanisms Underlying Aquaporin-4 Subcellular Mislocalization in Epilepsy

Extreme Membrane Tensile Loads Induce Half-Activation of the Thermosensitive TRPV1 Channel

How Shockwaves Open Tight Junctions of Blood–Brain Barrier: Comparison of Three Biomechanical Effects

Contact Info

Product

Resources

About