A reevaluation of veratridine as a tool for studying the depolarization-induced release of neurotransmitters from nerve endings.
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.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000378:metabolism; D007700:Kinetics; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects* / Q000502:physiology; D013696:Temperature; D014701:Veratridine / Q000494:pharmacology*; D014702:Veratrine / Q000031:analogs & derivatives*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D014702:Veratrine; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine