DOPAMINE D-1-LIKE RECEPTOR ACTIVATION EXCITES RAT STRIATAL LARGE ASPINY NEURONS IN-VITRO

The aim of this study was to elucidate electrophysiologically the acti ons of dopamine and SKF38393, a D-1-like dopamine receptor agonist, on the membrane excitability of striatal large aspiny neurons (cholinerg ic interneurons). Whole-cell and perforated patch-clamp recordings wer e made of striatal cholinergic neurons in rat brain slice preparations . Bath application of dopa mine (1-100 mu M) evoked a depolarization/i nward current with an increase, a decrease, or no change in membrane c onductance 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 curren t reversed at -42 mV, which suggested an involvement of a cation perme able channel. Change in external K+ concentration shifted the reversal potential as expected for E-K in low Na+ solution. The current observ ed in 2 mM Ba2+ -containing solution reversed at -28 mV. These actions of dopamine were mimicked by application of SKF38393 (1-50 mu M) or f orskolin (10 mu M), an adenylyl cyclase activator, and were blocked by SCH23390 (10 mu M) or SQ22536 (300 mu M), an inhibitor of adenylyl cy clase. These data indicate, first, that dopamine depolarizes the stria tal large aspiny neurons by a D-1-mediated suppression of resting K+ c onductance and an opening of a nonselective cation channel and, second , that both mechanisms are mediated by an adenylyl cyclase-dependent p athway.