Differential effects of potassium channel blockers on dopamine release from rat striatal slices.
The effects of different potassium channel blockers on tritiated dopamine [( 3H]DA) release were investigated in rat striatal slices in the presence of pargyline and nomifensine (10 microM each). 4-Aminopyridine (4-AP; 10 and 30 microM) and 3,4-diaminopyridine (3,4-DAP; 30 microM) markedly increased the basal tritium outflow, whereas tetraethylammonium (TEA; 100-1000 microM) was without effect. The facilitating effect of 4-AP (10 microM) on spontaneous release was Ca(2+)- and K(+)-dependent. Moreover, the 4-AP-induced increase in spontaneous release was abolished in the presence of tetrodotoxin, indicating that voltage-dependent Na+ channels were involved in the release mechanism. 4-AP (10 and 30 microM) induced a dose-dependent decrease in K(+)-evoked [3H]DA release. This effect was confirmed with 3,4-DAP (30 microM). When striatal slices were depolarized with veratridine (5 microM), these two aminopyridines increased the evoked release of [3H]DA. TEA increased both K(+)- and veratridine-evoked [3H]DA release. These biochemical results are consistent with electrophysiological differences between the mechanism of action of aminopyridines and that of TEA.
Rhône-Poulenc Santé, Centre de Recherche de Vitry-Alfortville, Département Biologie, Vitry-sur-Seine, France.
A
A
Boireau
F
F
Richard
V
V
Olivier
M
M
Aubeneau
J M
JM
Miquet
P
P
Dubédat
P
P
Laduron
A
A
Doble
J C
JC
Blanchard
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000077770:Amifampridine; D000818:Animals; D002412:Cations / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000187:drug effects; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D002412:Cations; D015221:Potassium Channels; D015222:Sodium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D000077770:Amifampridine; D004298:Dopamine