Dopamine acts on D2 receptors to increase potassium conductance in neurones of the rat substantia nigra zona compacta

Abstract

1. Intracellular recordings were made from neurones in the substantia nigra zona compacta in slices of rat mesencephalon in vitro. The majority of neurones fired action potentials spontaneously at 0.2-5.6 Hz. Dopamine, applied either by superfusion or from the tip of a pressurized pipette, prevented spontaneous action potential firing and hyperpolarized the membrane. 2. When the membrane potential was held negative to the threshold for action potential firing, the hyperpolarization evoked by dopamine was accompanied by a fall in input resistance. Under voltage clamp, dopamine produced an outward membrane current associated with an increase in membrane conductance. The effects of superfused dopamine on firing rate, membrane potential and membrane current were concentration dependent in the range 1-100 microM. 3. The reversal potential for the hyperpolarizations and the outward currents produced by dopamine was -109.7 +/- 1.7 mV (n = 12) when the potassium concentration was 2.5 mM and -74.0 +/- 5.0 mV (n = 4) when the potassium concentration was 10.5 mM. The change in reversal potentials in these and intermediate potassium concentrations was described by the Nernst equation. 4. The outward current induced by dopamine was reversibly reduced by barium (100-300 microM) and by high concentrations of tetraethylammonium (greater than or equal to 10 mM). Calcium-free solutions with cobalt (0.5-2 mM) did not reduce the current in response to dopamine during the first 5 min of their application. Currents and hyperpolarizations caused by dopamine were unaffected by tetrodotoxin (1 microM). 5. The hyperpolarization produced by dopamine was mimicked by the D2 receptor agonist quinpirole (LY 171555, 0.1-3 microM) and was blocked by the D2 receptor agonists domperidone and (-)-sulpiride. Agonists and antagonists at D1 receptors had no effect. 6. (-)-Sulpiride (30 nM-30 microM) produced a progressive shift to the right in the concentration-response curve to either dopamine or quinpirole. Schild analysis of the antagonism between (-)-sulpiride and quinpirole suggested competitive antagonism with a dissociation equilibrium constant for (-)-sulpiride of about 13 nM. 7. It is concluded that dopamine acts on D2 receptors on neurones of the rat substantia nigra pars compacta to increase the membrane potassium conductance.