KCC2 mediates NH4+ uptake in cultured rat brain neurons.
Elevated levels of NH4+ in the brain impair neuronal function. We studied the effects of NH4+ on postsynaptic inhibition of cultured rat brain neurons using whole cell recording under nominally HCO3- -free conditions. Application of NH4+ shifted the reversal potentials for spontaneous inhibitory postsynaptic currents and currents elicited by dendritic GABA applications in a positive direction because [Cl-]i increased. The positive shift of the reversal potentials of GABA-induced Cl- currents was equal on equimolar elevation of [NH4+]o or [K+]o, respectively. The NH4+-induced increase in [Cl-]i was reversed by an inhibitor of cation-anion cotransport, furosemide (0.1 mM), but not by bumetanide (0.01 mM) or by replacement of [Na+]o by Li+. We conclude that neuron-specific K-Cl cotransporter (KCC2) transports NH4+ similar to K+. Despite this fact, the small increase of [NH4+]o during metabolic encephalopathies will barely elevate [Cl-]i. However, an impairment of neuronal function may result because KCC2 provides a pathway to accumulate NH4+, and thereby, a continuous acid load to neurons.
Liu
Xiuxin
X
Institut für Physiologie und Pathophysiologie und Interdisziplinäres Zentrum für Neurowissenschaften, Universität Heidelberg, D-69120 Heidelberg, Germany.
Titz
Stefan
S
Lewen
Andrea
A
Misgeld
Ulrich
U
D000643:Ammonium Chloride / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D000096922:K Cl- Cotransporters
D000643:Ammonium Chloride; D027981:Symporters; D000096922:K Cl- Cotransporters