Abstract

In superfused striatal synaptosomes, previously unexposed to Ca2+ during isolation and superfusion, 1.25 mM Ca2+ evokes the release of [3H]dopamine. This Ca2+-evoked release is produced without elevating K+ (4.5 mM) before or after Ca2+ exposure, can be blocked by the Na+ channel antagonist tetrodotoxin, and modulated by dopamine (D2) receptor agonists and antagonists. We now present evidence that functional K+ channels regulate Ca2+-evoked [3H]dopamine release and may be necessary for the dopamine (D2) modulation of this release. The K+ channel blocker tetraethyl ammonium (TEA) could partially prevent D2 agonist (LY-171555) inhibition of Ca2+-evoked release in both olfactory tubercle and striatal synaptosomes. Another K+ channel blocker, 4-aminopyridine, also partially blocked dopamine (D2) agonist inhibition of release. When both 5 mM tetraethyl ammonium and 0.1 mM 4-aminopyridine were employed, by, dopamine (D2) inhibition of Ca2+-evoked [3H]dopamine release was prevented. However, with both K+ channel blockers present, only the initial portion of the release could be blocked by tetrodotoxin. These results are consistent with what might be expected if K+ channels were linked to dopamine (D2) receptors. In additional experiments we found that stimulation of adenylate cyclase by 1 microM forskolin with 0.25 mM 3-isobutyl-1-methylxanthine present potentiated Ca2+-evoked [3H]dopamine release but that this combination did not affect dopamine (D2) inhibition of [3H]dopamine release. Furthermore, although the protein alkylator n-ethylmaleimide could block dopamine (D2) inhibition of release, pertussis toxin, a specific inactivator of the inhibitory protein regulating adenylate cyclase, had little effect on dopamine (D2) inhibition. Therefore, dopamine (D2) inhibition of dopamine release may not be coupled to adenylate cyclase activity.