Volume-regulated anion channel

[4] VRACs have also been shown to participate in fundamental cellular processes other than basic volume regulation, such as cell proliferation, migration, and apoptosis.

For glutamate, when excitatory neurotransmitters are released and activates channels on surrounding neurons, it results in overactive depolarization, and increase in calcium ions, and eventually cellular apoptosis.

[17] Experiments have found that VRAC inhibitors were able to decrease the stroke-related release of excitatory neurotransmitters in the brain;[6] which means that VRACs are likely activated by the increase of cellular ATP and other molecules in astrocytes, and the release of glutamate by these cells causes the neurons around them to become depolarized, increase their calcium ion concentration, and undergo apoptosis.

Specifically, it is thought that the release of taurine from glia by VRACs is linked to systemic volume regulation in the osmosensing supraoptical nucleus (SON).

[18] Astrocytes were again studied in relation to this discovery, and they found that the cells readily respond to a hypertonic environment by releasing taurine through VRAC-like channels.

Based on these studies conducted on VRACs role in both excitotoxicity conditions and the regulation of the osmosensing supraoptical nucleus (SON), there are large implications for the actual influence this channel has on everyday neuronal activity.

Another important aspect of neurons to keep in mind is that potassium, chloride cotransporters (KCCs) are other proteins that are also part of the RVD process and are activated when cells undergo swelling.

[3][1] This is important to keep in mind because VRACs are not the only molecules present that aid in cell volume regulation, and recent research has shown that the likelihood that these two channels work cooperatively is high.

It is hoped that the study of this genetic disease ("TIMES syndrome"; see OMIM https://omim.org/entry/621056) may lead to increased understanding of the physiologic functions of VRACs and perhaps also to pharmacological modulation.

Basic outline of a VRAC in RVD.
Basic role of VRAC in RVD and Cell Apoptosis. This model is simplistic as it does not account for different LRRC8 protein subunits that make up the VRACs. It has been determined by Planells-Cases et al. that different subunit composition allows for specificity of VRACs (2015). This shown process is for RVD, but VRAC is also active in the observed cell shrinkage that occurs before apoptosis through the same release of anions and organic osmolytes.