{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T16:43:32Z","timestamp":1774284212246,"version":"3.50.1"},"reference-count":33,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurophysiology"],"published-print":{"date-parts":[[1999,10,1]]},"abstract":"<jats:p>The generation of activity-evoked extracellular alkaline shifts has been linked to the presence of external Ca<jats:sup>2+<\/jats:sup>or Ba<jats:sup>2+<\/jats:sup>. We further investigated this dependence using pH- and Ca<jats:sup>2+<\/jats:sup>-selective microelectrodes in the CA1 area of juvenile, rat hippocampal slices. In HEPES-buffered media, alkaline transients evoked by pressure ejection of RS-\u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) averaged \u223c0.07 unit pH and were calculated to arise from the equivalent net addition of \u223c1 mM strong base to the interstitial space. These alkaline responses were correlated with a mean decrease in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>of \u223c300 \u03bcM. The alkalinizations were abolished reversibly in zero-Ca<jats:sup>2+<\/jats:sup>media, becoming indiscernible at a [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>of 117 \u00b1 29 \u03bcM. Addition of as little as 30\u201350 \u03bcM Ba<jats:sup>2+<\/jats:sup>caused the reappearance of an alkaline response. In approximately one-fourth of slices, a persistent alkaline shift of \u223c0.03 unit pH was observed in zero-Ca<jats:sup>2+<\/jats:sup>saline containing EGTA. In HEPES media, addition of 300 \u03bcM Cd<jats:sup>2+<\/jats:sup>, 100 \u03bcM Ni<jats:sup>2+<\/jats:sup>, or 100 \u03bcM nimodipine inhibited the alkaline shifts by roughly one-half, one-third, and one-third, respectively, whereas Cd<jats:sup>+<\/jats:sup>and Ni<jats:sup>2+<\/jats:sup>in combination fully blocked the response. In bicarbonate media, by contrast, Cd<jats:sup>+<\/jats:sup>and Ni<jats:sup>2+<\/jats:sup>blocked only two-thirds of the response. In the presence of bicarbonate, Ni<jats:sup>2+<\/jats:sup>caused an unexpected enhancement of the alkalinization by \u223c150%. However, when the extracellular carbonic anhydrase was blocked by benzolamide, addition of Ni<jats:sup>2+<\/jats:sup>reduced the alkaline shift. These results suggested that Ni<jats:sup>2+<\/jats:sup>partially inhibited the interstitial carbonic anhydrase and thereby increased the alkaline responses. These data indicate that an activity-dependent alkaline shift is largely dependent on the entry of Ca<jats:sup>2+<\/jats:sup>or Ba<jats:sup>2+<\/jats:sup>via voltage-gated calcium channels. However, sizable alkaline transients still can be generated with little or no external presence of these ions. Implications for the mechanism of the activity-dependent alkaline shift are discussed.<\/jats:p>","DOI":"10.1152\/jn.1999.82.4.1902","type":"journal-article","created":{"date-parts":[[2017,12,25]],"date-time":"2017-12-25T05:25:37Z","timestamp":1514179537000},"page":"1902-1908","source":"Crossref","is-referenced-by-count":11,"title":["Effect of Divalent Cations on AMPA-Evoked Extracellular Alkaline Shifts in Rat Hippocampal Slices"],"prefix":"10.1152","volume":"82","author":[{"given":"S. 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