1. Pharmacological identification of inward current evoked by dopamine in rat subthalamic neurons in vitro
- Author
-
Zi Tao Zhu, Ke Zhong Shen, and Steven W. Johnson
- Subjects
Male ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Dopamine ,Action Potentials ,Pharmacology ,Guanosine Diphosphate ,Membrane Potentials ,Receptors, Dopamine ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Quinpirole ,Slice preparation ,GTP-Binding Proteins ,Subthalamic Nucleus ,Internal medicine ,Dopamine receptor D2 ,medicine ,Animals ,Neurons ,Dose-Response Relationship, Drug ,Chemistry ,Glutamate receptor ,Thionucleotides ,Rats ,Electrophysiology ,Endocrinology ,nervous system ,Guanosine 5'-O-(3-Thiotriphosphate) ,CNQX ,medicine.drug - Abstract
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 microM) produced a reversible concentration-dependent inward current (I(DA); 6-40 pA) with an EC(50) of 13 microM. 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 D(2) receptor agonist, mimicked the DA action more effectively than did the D(1) agonist SKF-38393. The D(2) antagonist sulpiride, but not the D(1) antagonist SCH-23390, blocked responses induced by DA. Intracellular application of G-protein inhibitor GDP-beta-S also suppressed I(DA). GTP-gamma-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 D(2)-like receptors which reduce a K(+) conductance.
- Published
- 2002