Ammonium influx pathways into astrocytes and neurones of hippocampal slices

作者：Kelly Tony; Rose Christine R^*

来源：Journal of Neurochemistry, 2010, 115(5): 1123-1136.

DOI：10.1111/j.1471-4159.2010.07009.x

• hepatic encephalopathy
• hyperammonaemia
• Na(+)
• K(+)-ATPase
• NKCC
• pH
• sodium

Ammonium (NH(4)(+)) is required to maintain pathways involved in shuttling metabolic precursors between astrocytes and neurones. Under hyperammonaemic conditions, increases in the cellular influx of NH(4)(+), and accompanying changes in ion concentrations, may contribute to disruptions in metabolism and neurotransmission. We investigated mechanisms of cellular NH(4)(+) influx in hippocampal slices by measuring acute NH(4)(+)/NH(3)-evoked changes in intracellular pH (pH(i)) and sodium ([Na(+)](i)). In both astrocytes and neurones, application of 5 mM NH(4)Cl for 30-45 min decreased pH(i) by 0.2-0.3 units, consistent with NH(4)(+) influx. In astrocytes, but not neurones, acidifications were accompanied by [Na(+)](i) increases of 25-30 mM. Glial [Na(+)](i) increases were blocked by bumetanide, suggesting that NH(4)(+)/NH(3) activated Na(+)-dependent, K(+), Cl(-) cotransport. Bumetanide also reduced NH(4)(+)/NH(3)-evoked acidifications in astrocytes. Neuronal acidifications were insensitive to bumetanide and inhibition of Cl(-)-dependent transport and K(+) channels, but were prevented by inhibition of Na(+), K(+)-ATPase with ouabain. Furthermore, ouabain reduced astrocyte acidifications. Our results suggest that following rapid elevation of NH(4)(+), Na(+), K(+)-ATPase is the major influx pathway for NH(4)(+) in neurones, whereas Na(+), K(+)-ATPase and Na(+)-dependent, K(+), Cl(-) cotransport mediate NH(4)(+) transport into astrocytes. The different mechanisms of NH(4)(+) influx in astrocytes and neurones may contribute to the different susceptibility of both cell types to acute hyperammonaemic conditions.

• 出版日期2010-12