Extracellular alkaline transients mediated by glutamate receptors in the rat hippocampal slice are not due to a proton conductance.

1. The ionic mechanism of extracellular alkaline transients mediated by alpha-amino-3-hydroxy-5-methylisoxazolate-4-propionic acid (AMPA) receptor channels was studied in the rat hippocampal slice (area CA1) by means of H(+)-, Ca(2+)- and Na(+)-selective microelectrodes. 2. Alkaline transients mediated by selective synaptic activation of AMPA receptors were coupled to a transient fall in extracellular Ca2+ ([Ca2+]o). 3. Removal of [Ca2+]o blocked the alkaline transient evoked by microinjection of AMPA, but had little effect on the simultaneous tetrodotoxin-resistant fall in extracellular Na+ ([Na+]o). 4. Alkaline transients evoked by microinjection of gamma-aminobutyric acid (GABA) were not affected by removal of [Ca2+]o. GABA had no effect on [Na+]o. 5. The present results indicate that activity-induced glutamatergic alkaline transients in the hippocampal slice are due to an influx of Ca2+, and not to a conductive movement of H+ ions across glutamate-gated cation channels.