Ammonium in nervous tissue: transport across cell membranes, fluxes from neurons to glial cells, and role in signalling

Most. but not all, animal cell membranes are permeable to NH3. the neutral. minority form of ammonium which is in equilibrium with the charged majorit y form NH4+. NH4+ crosses many cell membranes via ion channels or on membra ne transporters, and cultured mammalian astrocytes and glial cells of bee r etina take up NH4+ avidly, in the latter case on a Cl--cotransporter select ive for NH4+ over K+. In bee retina, a flux of ammonium from neurons to gli al cells is an essential component of energy metabolism which involves a fl ux of alanine from glial cells to neurons. In mammalian brain. both glutama te and ammonium are taken up preferentially by astrocytes and form glutamin e. Glutamine is transferred to neurons where it is deamidated to re-form gl utamate: the maintenance of this cycle appears to require a substantial flu x of ammonium from neurons to astrocytes. In addition to maintaining the gl ial cell content of fixed N (a 'bookkeeping' function), ammonium is expecte d to participate in the regulation of glial cell metabolism (a signalling F unction): it will increase conversion of glutamate to glutamine, and, by ac tivating phosphofructokinase and inhibiting the alpha -ketoglutarate dehydr ogenase complex. it will tend to increase the formation of lactate. (C) 200 1 Elsevier Science Ltd. All rights reserved.