γ‐Aminobutyric acid (GABA) evokes catecholamine (CA) secretion and enhances the stimulation‐evoked CA secretion via facilitation of Ca2+ entry in a Cl−‐dependent manner. The present study was designed to investigate further the ionic mechanism of modulation by GABA of CA secretion from adrenal medulla, using a primary culture of bovine chromaffin cells. Tetrodotoxin (TTX), a voltage‐sensitive Na+ channel blocker, reduced GABA‐evoked CA secretion. Inhibition of the sodium pump by ouabain or removal of extracellular K+ enhanced GABA‐evoked CA secretion in a TTX‐sensitive manner. Tetraethylammonium (TEA) and cesium, which are known to block some types of K+ channels, markedly enhanced GABA‐evoked CA secretion in a concentration‐related fashion. TEA‐induced enhancement of the GABA‐evoked CA secretion was attenuated by TTX or replacement of extracellular Na+ by choline. On the other hand, ouabain accelerated the effect of TEA. TEA and ouabain also enhanced GABA‐induced Ca2+ influx and accumulation of cytosolic Ca2+, assessed with 45Ca2+ uptake and quin2 fluorescence. Veratridine increased accumulation of cytosolic Ca2+ in a TTX‐sensitive manner. GABA facilitated the veratridine‐induced elevation of cytosolic Ca2+ even when the GABA‐induced rise of cytosolic Ca2+ levelled off. These results suggest the involvement of repetitive action potentials in modulation of GABA by Ca2+ mobilization and, as a consequence, of the CA secretion in chromaffin cells.

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