Studies on the role of Na+, K+ and Cl- ion permeabilities in K+-induced release of 3H-noradrenaline from rat brain slices and synaptosomes and in its presynaptic alpha-adrenergic modulation.

Abstract

Possible ionic mechanisms by which activation of presynaptic α-adrenoceptors might inhibit the K+-induced release of 3H-noradrenaline from superfused rat cerebral cortex slices or synaptosomes were investigated. (1) 4-Aminopyridine (4-AP), a blocker of K+-permeability, enhanced the release of 3H-noradrenaline from cortex slices induced by 13 mM K+ in a concentration-dependent manner; 1 mM 4-AP caused an enhancement by 400%. By itself, 4-AP also induced a Ca2+-dependent release of 3H-noradrenaline; the release caused by 1 mM 4-AP was of a similar magnitude as that caused by 13 mM K+. (2) Tetrodotoxin (TTX), a blocker of Na+-permeability, concentration-dependently inhibited the release of 3H-noradrenaline induced by 13 mM K+; 0.3 μM TTX caused an inhibition by 90%. (3) The enhancing effect of 4-AP and the inhibitory effect of TTX on K+-induced 3H-noradrenaline release were inversely related to the K+-concentration used to stimulate release. (4) The release of 3H-noradrenaline from synaptosomes induced by 6–10 mM K+ was also enhanced by 4-AP and inhibited by TTX. (5) In Cl−-free medium the baseline tritium efflux was increased to about 3 times that found in normal medium. The release of 3H-noradrenaline induced by 13 mM K+ was enhanced by about 40% in Cl−-free medium. (6) Both the inhibitory effect of the α-receptor agonist oxymetazoline and the enhancing effect of the antagonist phentolamine on K+-induced 3H-noradrenaline release were decreased by 4-AP (1 mM). The effect of oxymetazoline was fully restored, despite the presence of 4-AP, when the Ca2+-concentration in the medium was lowered from 1.2 to 0.1 mM. Under these low Ca2+ conditions the effect of phentolamine was partially restored. (7) No change in presynaptic modulation of K+-induced 3H-noradrenaline release by oxymetazoline and phentolamine was observed when TTX (0.3 μM) was present in the medium. Moreover, 3H-noradrenaline release induced by increasing Na+-permeability with veratrine was effectively modulated. (8) Effective modulation of K+-induced 3H-noradrenaline release by oxymetazoline and phentolamine was also observed in Cl−-free medium.