Regulation of postsynaptic Ca2+ influx in hippocampal CA1 pyramidal neurons via extracellular carbonic anhydrase.
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 pH(e) 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 pH(e) 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 pH(e) shifts. The data also suggest that Ca2+ transients are influenced by additional mechanisms sensitive to shifts in pH(e).
Fedirko
Nataliya
N
Department of Neurosurgery, New York University School of Medicine, New York, New York 10016, USA.
Avshalumov
Marat
M
Rice
Margaret E
ME
Chesler
Mitchell
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D045604:Extracellular Fluid / Q000201:enzymology* / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D017966:Pyramidal Cells / Q000201:enzymology* / Q000378:metabolism; D051381:Rats
D002256:Carbonic Anhydrases; D002118:Calcium