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 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.
Zhu
Zi-Tao
ZT
Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR 97201, USA.
Shen
Ke-Zhong
KZ
Johnson
Steven W
SW
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004298:Dopamine / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000502:physiology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D013873:Thionucleotides / Q000502:physiology
D011954:Receptors, Dopamine; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); D019204:GTP-Binding Proteins; D004298:Dopamine