Voltage-Sensitive Ca²⁺ Channels in Rat Brain Neocortical Noradrenergic Nerve Terminals

Abstract

In rat cerebral cortex slices we investigated the Ca²⁺ dependency of noradrenaline release and the influence of inorganic and organic Ca²⁺ antagonists. Slices were prein-cubated with ³H-noradrenaline and then superfused with noradrenaline-free medium. Release of ³H-noradrenaline was elicited by electrical pulses. The stimulation-evoked release was dependent on the external Ca²⁺ concentration and was inhibited by Co²⁺, Co²⁺ and Mg²⁺ in a concentration-related manner. These results indicate that electrically stimulated noradrenaline release depends on the Ca²⁺ influx after opening of voltage-sensitive Ca²⁺ channels. Organic Ca²⁺ antagonists were used in concentrations which had no major influence on the basal release rate. Of the drugs tested (bepridil, diltiazem, flunarizine, nimodipine, isradipine, prenylamine, verapamil) only flunarizine and nimodipine showed a minor inhibition of the stimulation-evoked release, which was less than 20% at 1 μmol/l. With nimodipine 10 μmol/l, there was a 6 % facilitation of release. All other drugs except flunarizine and verapamil caused a slight facilitation of the stimulation-evoked release. The results provide evidence that the organic Ca²⁺ channel antagonists investigated do not or only minimally interfere with the noradrenergic nerve terminal Ca²⁺ channels in a tissue slice preparation. The release-facilitating effects of most organic Ca²⁺ antagonists cannot be interpreted by the present results.