Amino acid osmolytes in regulatory volume decrease and isovolumetric regulation in brain cells: Contribution and mechanisms

Brain adaptation to hyposmolarity is accomplished by loss of both electroly tes and organic osmolytes, including amino acids, polyalcohols and methylam ines. 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 vol ume regulation, in conditions of sudden hyposmosis, when cells respond by a ctive regulatory volume decrease (RVD) or after gradual exposure to hyposmo tic solutions, a condition where cell volume remains unchanged, named isovo lumetric regulation (IVR). The amino acid efflux pathway during RVD is pass ive and is similar in many respects to the volume-activated anion pathway. The molecular identity of this pathway is still unknown, but the anion exch anger and the phospholemman are good candidates in certain cells. The activ ation trigger of the osmosensitive amino acid pathway is unclear, but intra cellular ionic strength seems to be critically involved. Tyrosine protein k inases markedly influence amino acid efflux during RVD and may play an impo rtant role in the transduction signaling cascades for osmosensitive amino a cid fluxes. During IVR, amino acids, particularly taurine are promptly rele ased with an efflux threshold markedly lower than that of K+, emphasizing t heir contribution (possibly as well as of other organic osmolytes) vs inorg anic ions, in the osmolarity range corresponding to physiopathological cond itions. Amino acid efflux also occurs in response to isosmotic swelling as that associated with ischemia or trauma. Characterization of the pathway in volved 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 respons e to stimuli concurrent with swelling, such as depolarization or intracellu lar Ca++ elevation. Copyright (C) 2000 S. Karger AG Basel.