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  • Title: A reevaluation of veratridine as a tool for studying the depolarization-induced release of neurotransmitters from nerve endings.
    Author: Levi G, Gallo V, Raiteri M.
    Journal: Neurochem Res; 1980 Mar; 5(3):281-95. PubMed ID: 6103519.
    Abstract:
    The effect of veratridine on neurotransmitter release was studied using rat brain synaptosomes superfused at 37 degrees C. Veratridine (5-75 microM) caused a concentration-dependent release of [3H]GABA from prelabeled synaptosomes in the presence of 2.7 mM Ca2+. In the whole range of veratridine concentrations, the release of [3H]GABA elicited by the drug was substantially increased rather than decreased in the absence of Ca2+ or with Ca2+ concentrations of 0.45 and 0.9 mM. The release of the amino acid was inhibited more by 5.4 mM than by 2.7 mM Ca2+. The effect on endogenous (chemically measured) GABA was similar to that on [3H]GABA. The inhibitory effect of Ca2+ on the veratridine-induced release of [3H]GABA was consistently seen in a variety of experimental conditions except one, namely when the experiment was run at room temperature (22-23 degrees C) rather than at physiological temperature (37 degrees C). In fact, at 22-23 degrees C the release of GABA evoked by the alkaloid was somewhat potentiated by Ca2+. At 37 degrees C, glutamate appeared to behave similarly to GABA, whereas the veratridine-induced release of [3H]noradrenaline and [3H]dopamaine was largely Ca2+-dependent. The mechanism of the release of transmitters elicited by veratridine is discussed. It is concluded that the evoked release of GABA and glutamate is due more to the veratridine-induced depolarization (Na+ influx) than to the accompanying influx of Ca2+, and it is suggested that the inhibitory effect of Ca2+ on the overall release of amino acids is due to the antagonism exerted by the divalent cation on the veratridine action at the Na+ channel. In contrast, in the case of catecholamines, the influx of Ca2+ would have a prominent role in triggering exocytotic release, whereas the depolarization itself would have slight or no importance.
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