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.

Do silent dopaminergic neurons exist in rat substantia nigra in vivo?

“…to inhibit the spontaneous activity of dopaminergic neurons by activating somatodendritic D 2 -like autoreceptors. 2,29,35,52 Supplementary doses of apomorphine were administered periodically to maintain the complete inhibition of spontaneous activity throughout the subsequent recording period, which typically lasted about 1 h. In some experiments, apomorphine was continuously infused through a femoral catheter at 20 µg/kg/min to maintain the inhibition. During the period of effective inhibition, recording electrodes were advanced at 2 µm/s to search for dopaminergic neurons identified by antidromic responses elicited by either striatal or MFB stimulation at 1.0 mA, a value chosen on the basis of previous experiments (e.g., Refs 48, 49 and 53) to be sufficient to activate antidromically a large proportion of dopaminergic neurons.…”

“…This leads to the opening of potassium channels, which not only hyperpolarizes the somatodendritic region, but also decreases its membrane resistance and increases the electrotonic length of the neuron. 35 This would be expected to decrease the invasion of the dendrites by the spike, whether active 31 or passive. Since the size of the field potential around a neuron depends in large part on the extent to which dendrites distal to the cell body are depolarized, 36 autoreceptor blockade by D 2 -like antagonists might increase the size of the extracellular field as a consequence of increased membrane resistance and decreased electrotonic length of the cell.…”

Somatodendritic dopamine release: recent mechanistic insights

“…Williams and co-workers pioneered the use of D2 DA autoreceptor-dependent currents as a 'biosensor' for evoked DA release in the SNc and VTA [23,24,26,55,69,72]. The detected currents arise from the DA-dependent activation of D2 autoreceptors, which are linked to G-protein-coupled inwardly rectifying K þ (GIRK) channels in DA neurons [73][74][75][76]. These are referred to as D2-dependent inhibitory postsynaptic currents (D2-IPSCs; figure 2b, right panel).…”

Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

“…The presumed DAergic neurons were identified based on their location within the slice and electrophysiologic and pharmacologic properties, and thus by the presence of regular spontaneous firing activity, wide action potential Ͼ 1.1 msec (as measured by the interval occurring between the initiation of spike's depolarization and the corresponding potential in the repolarizing phase), time-dependent I h in response to hyperpolarizing voltage steps, and hyperpolarization caused by DA (3-30 mol/L) (Grace and Onn 1989;Lacey et al 1987;Mercuri et al 1995). Only neurons meeting these criteria were studied.…”