Comparison between electrically evoked and potassium-induced (3)H-noradrenaline release from rat neocortex slices: Role of calcium ions and transmitter pools.
In this study (3)H-noradrenaline (NA) release from rat neocortex slices evoked by electrical field-stimulation (1 Hz, 12 mA, 2 msec) was compared with that induced by K(+)-depolarization (13-30 mM K(+)) under similar experimental conditions, with a particular emphasis on the role of external Ca(2+) and the releasable transmitter pool(s). Not only (3)H-NA release evoked by electrical stimulation but also that induced by 13 mM K(+) was almost completely blocked by 0.3 ?M tetrodotoxin (TTX). Release induced by 20 mM K(+) appeared to be less sensitive to TTX. Thus, under relatively mild stimulation conditions, the activation of sodium channels appears to be involved in (3)H-NA release elicited by both stimuli. The electrically evoked (3)H-NA release increased sigmoidally with the external Ca(2+)-concentration up to 1.2 mM. In contrast, (3)H-NA release induced by 13-20 mM K(+) reached a maximal value at 0.6-0.9 mM Ca(2+) and gradually decreased at higher Ca(2+)-concentrations. The Ca(2+)-antagonist D-600 (1-30 ?M) did not inhibit electrically evoked release, while K(+)-induced (3)H-NA release was dose-dependently reduced. Upon repetitive K(+)-depolarization a strong depression of (3)H-NA release could be demonstrated, while this phenomenon did not occur with repeated electrical stimulation. Moreover, a previous K(+)-induced (partial) depletion of (3)H-NA stores did not affect the release evoked by electrical pulses and vice versa. Taken together these data are compatible with a much stronger activation of Ca(2+)-channels and a larger vesicle mobilizing capacity in case of electrical stimulation at physiological frequencies compared to sustained depolarization with moderate K(+)-concentrations.
Schoffelmeer
A N
AN
Department of Pharmacology, Free University, Medical Faculty, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Wemer
J
J
Mulder
A H
AH