RELATIONSHIP BETWEEN CA2+-DEPENDENT AND INDEPENDENT RELEASE OF [H-3]GABA EVOKED BY HIGH K+, VERATRIDINE OR ELECTRICAL-STIMULATION FROM RAT CORTICAL SLICES

Abstract— It has been reported that the release of GABA by high K+ is Ca2+‐dependent while release induced by veratridine or electrical stimulation has been frequently found to be independent of Ca2+. To see the source of Ca2+‐dependent and independent release of GABA, cortical slices which had accumulated [3H]GABA were exposed to 50 mm‐K+ or 50 μm‐veratridine for 48min. In the presence of Ca2+ the 2 agents released approx the same amount of [3H]GABA but tetrodotoxin (TTX) abolished release induced only by veratridine, while omission of Ca2+ reduced release induced only by 50mm‐K+. Pre‐exposure of the slices for 48min to 50mm‐K+ in the presence of Ca2+ reduced the second release by 50mm‐K+ by 77% and that by veratridine by 74%, suggesting that in the presence of Ca2+ the 2 depolarizing agents release [3H]GABA from the same pool. Pre‐exposure to 50mm‐K+ in the absence of Ca2+ reduced the second release by 50mm‐K+ or by veratridine only by 37 and 27% respectively, indicating that most of the reduction in release was the result of a depletion of releasable [3H]GABA stores. The second exposure to 50mm‐K+ in the absence of Ca2+ reduced the evoked release further, while exposure to veratridine in the absence of Ca2+, after depletion of the stores, enhanced release 2.7 times. Electrical stimulation (64 Hz, 2 ms, 40 mA, alternating polarity) during 24min in the presence of Ca” caused an initial 5‐fold increase in efflux, which declined subsequently. In the absence of Ca2+, instead of a rapid increase, a slow but smaller increase in the efflux of [3H]GABA was found. TTX almost completely abolished the electrically evoked increase in release. Pre‐treatment with 50mm‐K+ reduced the electrically evoked release by 94% but electrical stimulation in the absence of Ca2+ after depletion of releasable stores doubled this release. Results suggest that in the presence of Ca2+, high K+, veratridine and electrical stimulation release [3H]GABA from the same Ca2+‐dependent store, but in the absence of Ca2+ veratridine and electrical stimulation enhance the release from a Ca2+‐independent store, probably as a result of an increased influx of Na+. Copyright © 1979, Wiley Blackwell. All rights reserved