期刊
JOURNAL OF NEUROSCIENCE
卷 27, 期 5, 页码 1167-1175出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3535-06.2007
关键词
benzolamide; Fluo-5F; ion-selective microelectrode; stratum radiatum; NMDA receptor; APV
资金
- NINDS NIH HHS [NS36362, R01 NS036362, R01 NS032123, R56 NS036362, R56 NS032123, NS32123] Funding Source: Medline
Synchronous neural activity causes rapid changes of extracellular pH(pH(e)) in the nervous system. In the CA1 region of the hippocampus, stimulation of the Schaffer collaterals elicits an alkaline pH(e) transient in stratum radiatum that is limited by extracellular carbonic anhydrase (ECA). When interstitial buffering is diminished by inhibition of ECA, the alkalosis is enhanced and NMDA receptor (NMDAR)-mediated postsynaptic currents can be augmented. Accordingly, the dendritic influx of Ca2+ elicited by synaptic excitation may be expected to increase if ECA activity were blocked. We tested this hypothesis in the CA1 stratum radiatum of hippocampal slices from juvenile rats, using extracellular, concentric pH-and Ca2+-selective microelectrodes with response times of a few milliseconds, as well as Fluo-5F imaging of intracellular Ca2+ transients. Brief stimulation of the Schaffer collaterals elicited an alkaline pHe transient, a transient decrease in free extracellular Ca2+ concentration ([Ca2+](e)), and a corresponding transient rise in free intracellular Ca2+ concentration ([Ca2+](i)). Inhibition of ECA with benzolamide caused a marked amplification and prolonged recovery of the pHe and [Ca2+](e) responses, as well as the dendritic [Ca2+](i) transients. The increase in amplitude caused by benzolamide did not occur in the presence of the NMDAR antagonist APV, but the decay of the responses was still prolonged. These results indicate that ECA can shape dendritic Ca2+ dynamics governed by NMDARs by virtue of its regulation of concomitant activity-dependent pHe shifts. The data also suggest that Ca2+ transients are influenced by additional mechanisms sensitive to shifts in pHe.
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