Pharmacological identification of inward current evoked by dopamine in rat subthalamic neurons in vitro

Dopaminergic mechanisms in the subthalamic nucleus (STN) are implicated in the pathophysiology of Parkinson's disease. Here, electrophysiological responses of STN neurons to dopamine (DA) were investigated by using whole-cell patch-clamp recordings in the rat brain slice preparation. Under current-clamp, DA depolarized membrane potential and increased the frequency of spontaneous action potentials of STN neurons. Under voltage-clamp, DA (3-300 μM) produced a reversible concentration-dependent inward current (I_DA; 6-40 pA) with an EC₅₀ of 13 μM. This DA-induced current had a negative slope conductance which reversed at -102 mV. It was partially reduced by barium and by superfusion with an elevated concentration of extracellular K⁺. Moreover, TTX and glutamate receptor antagonists (CNQX and AP5) did not significantly affect the DA responses, indicating that I_DA is not dependent upon afferent synaptic activity in the STN. Quinpirole, a D₂ receptor agonist, mimicked the DA action more effectively than did the D₁ agonist SKF-38393. The D₂ antagonist sulpiride, but not the D₁ antagonist SCH-23390, blocked responses induced by DA. Intracellular application of G-protein inhibitor GDP-β-S also suppressed I_DA. GTP-γ-S, added to the pipette solution, evoked a sustained inward shift in the absence of DA. These results suggest that DA increases the activity of STN neurons via activation of G-protein-coupled D₂-like receptors which reduce a K⁺ conductance.