Dopamine D₁-Like Receptor Activation Excites Rat Striatal Large Aspiny Neurons<i>In Vitro</i>

Abstract

The aim of this study was to elucidate electrophysiologically the actions of dopamine and SKF38393, a D 1 -like dopamine receptor agonist, on the membrane excitability of striatal large aspiny neurons (cholinergic interneurons). Whole-cell and perforated patch-clamp recordings were made of striatal cholinergic neurons in rat brain slice preparations. Bath application of dopamine (1–100 μ m ) evoked a depolarization/inward current with an increase, a decrease, or no change in membrane conductance in a dose-dependent manner. This effect was antagonized by SCH23390, a D 1 -like dopamine receptor antagonist. The current–voltage relationships of the dopamine-induced current determined in 23 cells suggested two conductances. In 10 cells the current reversed at −94 mV, approximately equal to the K + equilibrium potential ( E K ); in three cells the I – V curves remained parallel, whereas in 10 cells the current reversed at −42 mV, which suggested an involvement of a cation permeable channel. Change in external K + concentration shifted the reversal potential as expected for E k in low Na + solution. The current observed in 2 m m Ba 2+ -containing solution reversed at −28 mV. These actions of dopamine were mimicked by application of SKF38393 (1–50 μ m ) or forskolin (10 μ m ), an adenylyl cyclase activator, and were blocked by SCH23390 (10 μ m ) or SQ22536 (300 μ m ), an inhibitor of adenylyl cyclase. These data indicate, first, that dopamine depolarizes the striatal large aspiny neurons by a D 1 -mediated suppression of resting K + conductance and an opening of a nonselective cation channel and, second, that both mechanisms are mediated by an adenylyl cyclase-dependent pathway.