PHARMACOLOGICAL EVIDENCE FOR THE POSSIBLE INVOLVEMENT OF REPETITIVE ACTION-POTENTIALS IN FACILITATION BY GABA OF CATECHOLAMINE SECRETION IN BOVINE ADRENAL CHROMAFFIN CELLS

1 gamma-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. 2 Tetrodotoxin (TTX), a voltage-sensitive Na+ channel blocker, reduced GABA-evoked CA secretion. 3 Inhibition of the sodium pump by ouabain or removal of extracellular K+ enhanced GABA-evoked CA secretion in a TTX-sensitive manner. 4 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. 5 TEA and ouabain also enhanced GABA-induced Ca2+ influx and accumulation of cytosolic Ca2+, assessed with Ca-45(2+) uptake and quin2 fluorescence. 6 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. 7 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.