Amino Acid Osmolytes in Regulatory Volume Decrease and Isovolumetric Regulation in Brain Cells: Contribution and Mechanisms

Abstract

Brain adaptation to hyposmolarity is accomplished by loss of both electrolytes and organic osmolytes, including amino acids, polyalcohols and methylamines. In brain in vivo, the organic osmolytes account for about 35% of the total solute loss. This review focus on the role of amino acids in cell volume regulation, in conditions of sudden hyposmosis, when cells respond by active regulatory volume decrease (RVD) or after gradual exposure to hyposmotic solutions, a condition where cell volume remains unchanged, named isovolumetric regulation (IVR). The amino acid efflux pathway during RVD is passive and is similar in many respects to the volume-activated anion pathway. The molecular identity of this pathway is still unknown, but the anion exchanger and the phospholemman are good candidates in certain cells. The activation trigger of the osmosensitive amino acid pathway is unclear, but intracellular ionic strength seems to be critically involved. Tyrosine protein kinases markedly influence amino acid efflux during RVD and may play an important role in the transduction signaling cascades for osmosensitive amino acid fluxes. During IVR, amino acids, particularly taurine are promptly released with an efflux threshold markedly lower than that of K⁺, emphasizing their contribution (possibly as well as of other organic osmolytes) vs inorganic ions, in the osmolarity range corresponding to physiopathological conditions. Amino acid efflux also occurs in response to isosmotic swelling as that associated with ischemia or trauma. Characterization of the pathway involved in this type of swelling is hampered by the fact that most osmolyte amino acids are also neuroactive amino acids and may be released in response to stimuli concurrent with swelling, such as depolarization or intracellular Ca⁺⁺ elevation.

Osmotic swelling-provoked release of organic osmolytes in human intestinal epithelial cells

“…We report a release pathway for organic osmolytes in intestine 407 epithelial cells, distinct from the compensatory anion efflux reported previously (53,55,57) and regulated by PKC. Hyposmotic release of organic osmolytes such as taurine, betaine, and inositol has been observed in many different cell models (2,3,12,17,25,45,46). Unlike chloride ions, which can have additional effects on enzyme activity, membrane potential, and, in muscle and nerve cells, the generation of action potentials, these organic osmolytes do not affect other cellular functions, making them especially suitable for volume regulation (2,13).…”

“…In excitable cells, these metabolites were found to be the major osmolytes released (41,45). Taurine especially has been implicated as an osmolyte involved in volume regulation (1,10,19).…”

Taurine Release by Astrocytes Modulates Osmosensitive Glycine Receptor Tone and Excitability in the Adult Supraoptic Nucleus

“…2c,d), indicating that taurine is a specific mediator of the tonic GlyR tone on SON neurons. and that taurine efflux through these channels plays a key role in the protective regulatory volume decrease response that follows hypotonicity-induced swelling (Olson and Li, 2000;Pasantes-Morales et al, 2000). To determine whether VRACs mediate the taurine efflux responsible for tonic GlyR tone in the SON, we examined the effects of bath applying the selective VRAC inhibitor DCPIB (butanoic acid) (He et al, 2012).…”

Hepatic encephalopathy: An approach to its multiple pathophysiological features

“…In particular, these include a decrease in the extracellular osmotic pressure [73] and the accumulation of excitatory amino acids [74] . After the initial phase of swelling, cells, particularly astrocytes, actively down��regulate their vol�� ume by regulatory volume decrease (RVD) and by a net release of KCl, taurine and other amino acids [74,75] ; in this way, EC� volume can return to normal values. Even later, when glia become reactive, astrogliosis may result in the formation of additional and persistent diffusion barri�� ers formed�� for example�� by the hypertrophy of fine glial processes or by an accumulation of macromolecules in the EC� (e.g., extracellular matrix proteins and cytokines) produced by neurons and glia [76] .…”