REGULATORY VOLUME DECREASE IN CULTURED ASTROCYTES .2. PERMEABILITY PATHWAY TO AMINO-ACIDS AND POLYOLS

The permeability of the hyposmolarity-activated pathway to amino acids and polyols in cultured astrocytes was examined following the change in rate and direction of regula tory volume decrease (RVD) when the ex tracellular concentration of the osmolytes was increased to reverse th eir intracellular-extracellular concentration gradient. Activation of the pathway by swelling would allow those permeable osmolytes to enter the cell and inhibit RVD. The pathway was found to be permeable to ne utral amino acids, with beta-amino acids (beta-alanine = taurine gamma -aminobutyric acid) more permeable than alpha-amino acids. Glycine, al anine, threonine, phenylalanine, and asparagine, but not glutamine, we re permeable through this pathway. Aspartate was more permeable than g lutamate, and K+ and not Na+ must be the accompanying cation. Basic am ino acids were excluded. The dimension of the amino acid pore activate d by hyposmolarity seems to be at the limit of glutamate-glutamine siz e. Influx rather than efflux of amino acids was observed when extracel lular concentration was greater than intracellular concentration, with differences in the amount accumulated by cells correlating with their efficiency as RVD blockers. Influx of taurine (as representative of p ermeable amino acids) was inhibited by the Cl- channel blockers/exchan gers 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (40%) and dipyri damole (85%), and it is suggested that amino acids permeate through an anion channel. Sorbitol and mannitol, but not inositol, exhibited a s mall inhibitory effect on the later phase of RVD, whereas inositol sli ghtly accelerated RVD.