期刊
NEUROCHEMICAL RESEARCH
卷 38, 期 11, 页码 2364-2374出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-013-1149-2
关键词
Astrocytes; Carbamazepine; Energy metabolism; NBCe1; pH(i); Potassium; Valproic acid
资金
- National Natural Science Foundation of China [31171036]
Neuronal excitation leads to an increase of the extracellular K+ concentration ([K+](o)) in brain. This increase has at least two energy-consuming consequences: (1) a depolarization-mediated change in intracellular pH (pH(i)) in astrocytes due to depolarization-mediated increased activity of the acid-extruding Na+/bicarbonate transporter NBCe1 (driven by secondary active transport, supported by ion gradients established by the Na+, K+-ATPase); and (2) activation of cellular reuptake of K+ mediated by the Na+, K+-ATPase in both neurons and astrocytes. Astrocytic, but not neuronal increase in NBCe1 activity and pH(i) is also seen after chronic treatment with either of the two anti-bipolar drugs carbamazepine or valproic acid. The third 'classical' anti-bipolar drug, 'lithium' increases astrocytic pH(i) by a different mechanism (stimulation of the acid extruding Na+/H+ exchanger NHE1). The acid extruder fluxes, which depend upon the change in pH(i) per time unit (Delta pH(i)/Delta t) and intracellular buffering power, have not been established in most of these situations. Therefore their stimulatory effects on energy metabolism has not been quantitated. This has been done in the present study in cultured mouse astrocytes. pH(i) was determined using the fluorescent pH-sensitive indicator BCECF-AM and an Olympus IX71 live cell imaging fluorescence microscope. Molar acid extrusion fluxes (indicating transporter activity) were determined as pH(i) changes/min during recovery after acid-loading with NH3/NH4 (+), NBCe1 mRNA and protein expression in the cultured cells by, respectively RT-PCR and Western blotting. Drug-induced up-regulation of acid extrusion flux was slow and less than physiologically seen after increase in K+ concentration. Energetically, K+ uptake is much costlier than NBCe1 activity.
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