KCl-induced calcium-independent release of endogenous dopamine from rat brain slices

Effects of the absence of calcium on the KCl- and electrical stimulation-induced releases of endogenous dopamine (DA) from rat brain slices were studied and the findings were compared with the effects on the release of endogenous noradrenaline (NA). DA and NA were extracted by the aluminum-adsorption method and assayed electrochemically by high-performance liquid chromatography. KCl, 15 mM, induced a significant increase in the release of DA from both the striatum and the hypothalamus, even in the Ca2+-free medium containing 1 mM EGTA. In the normal medium, the KCl-induced release of DA was concentration-dependent (15, 30 and 50 mM), while that in the Ca2+-free medium showed a plateau at 30 mM of KCl. The release of DA induced by electrical stimulation (10 cycles/s, 2 ms, 30 mA, for 5 min) was abolished in the Ca2+-free medium as was NA induced by both KCl and electrical stimulation. Nomifensine, 10 microM, a DA transport inhibitor, abolished the 15 mM KCl-induced release of DA in the Ca2+-free medium. On the other hand, the release of DA induced by electrical stimulation was considerably enhanced by nomifensine. Therefore, the mode of DA release induced by KCl sometimes differed from that induced by electrical stimulation. The present results also suggest that DA released by KCl in the Ca2+-free medium originates from cytoplasmic DA storage sites, through a carrier-mediated process.