Alpha1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice

J. Grenhoff, H. A. North, Steven Johnson

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Previous studies have indicated excitatory adrenergic effects on midbrain dopamine systems. To investigate the cellular mechanisms, intracellular recordings were made from neurons in perfused, oxygenated slices of male rat midbrain. Electrophysiological and pharmacological parameters were used to identify cells as principal (presumably dopaminergic) neurons as opposed to secondary (presumably GABAergic) neurons in the substantia nigra zona compacta and the ventral tegmental area. Noradrenalin (10-100 μM) hyperpolarized 57% of all principal cells and depolarized 36%. Sulpiride (100-1000 nM), a dopamine D2 receptor antagonist, completely blocked noradrenalin-induced hyperpolarizations (six of six cells). In sulpiride, noradrenalin depolarized 58% of all principal neurons and had no effect in 42%; this effect was mimicked by the α-adrenergic agonist phenylephrine (10-30 μM) which depolarized 43 of 72 cells. The α1 receptor antagonist prazosin (30-100 nM) completely blocked the membrane depolarization produced by either noradrenalin or phenylephrine in all cells tested, whereas α2- and β-adrenergic agents had no effect. In voltage clamp, phenylephrine evoked an inward current (at -60 mV) and reduced cord conductance by 0.81 ± 0.14 nS (n = 4). Inward current evoked by phenylephrine became outward at -96 ± 8 mV, which is near the membrane reversal potential for potassium as predicted by the Nernst equation. Phenylephrine also depolarized secondary cells and increased the frequency of spontaneous GABA(A) receptor-mediated postsynaptic potentials recorded in both principal and secondary cells. We conclude that stimulation of α1-adrenergic receptors depolarizes principal (dopamine) neurons by reducing membrane conductance for potassium, but this effect is modulated by the increase in frequency of spontaneous inhibitory postsynpatic potentials evoked by stimulation of α1-adrenergic receptors located on local interneurons.

Original languageEnglish (US)
Pages (from-to)1707-1713
Number of pages7
JournalEuropean Journal of Neuroscience
Volume7
Issue number8
DOIs
StatePublished - 1995

Fingerprint

Dopaminergic Neurons
Mesencephalon
Adrenergic Agents
Phenylephrine
Norepinephrine
Sulpiride
Adrenergic Receptors
Potassium
Neurons
GABAergic Neurons
Adrenergic Agonists
Synaptic Potentials
Ventral Tegmental Area
Membranes
Prazosin
Herpes Zoster
Interneurons
GABA-A Receptors
Evoked Potentials
Membrane Potentials

Keywords

  • Interneuron
  • Noradrenalin
  • Phenylephrine
  • Potasium current
  • Substantia nigra
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Alpha1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice. / Grenhoff, J.; North, H. A.; Johnson, Steven.

In: European Journal of Neuroscience, Vol. 7, No. 8, 1995, p. 1707-1713.

Research output: Contribution to journalArticle

@article{a2c8a34f016e47fd906530647f8db532,
title = "Alpha1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice",
abstract = "Previous studies have indicated excitatory adrenergic effects on midbrain dopamine systems. To investigate the cellular mechanisms, intracellular recordings were made from neurons in perfused, oxygenated slices of male rat midbrain. Electrophysiological and pharmacological parameters were used to identify cells as principal (presumably dopaminergic) neurons as opposed to secondary (presumably GABAergic) neurons in the substantia nigra zona compacta and the ventral tegmental area. Noradrenalin (10-100 μM) hyperpolarized 57{\%} of all principal cells and depolarized 36{\%}. Sulpiride (100-1000 nM), a dopamine D2 receptor antagonist, completely blocked noradrenalin-induced hyperpolarizations (six of six cells). In sulpiride, noradrenalin depolarized 58{\%} of all principal neurons and had no effect in 42{\%}; this effect was mimicked by the α-adrenergic agonist phenylephrine (10-30 μM) which depolarized 43 of 72 cells. The α1 receptor antagonist prazosin (30-100 nM) completely blocked the membrane depolarization produced by either noradrenalin or phenylephrine in all cells tested, whereas α2- and β-adrenergic agents had no effect. In voltage clamp, phenylephrine evoked an inward current (at -60 mV) and reduced cord conductance by 0.81 ± 0.14 nS (n = 4). Inward current evoked by phenylephrine became outward at -96 ± 8 mV, which is near the membrane reversal potential for potassium as predicted by the Nernst equation. Phenylephrine also depolarized secondary cells and increased the frequency of spontaneous GABA(A) receptor-mediated postsynaptic potentials recorded in both principal and secondary cells. We conclude that stimulation of α1-adrenergic receptors depolarizes principal (dopamine) neurons by reducing membrane conductance for potassium, but this effect is modulated by the increase in frequency of spontaneous inhibitory postsynpatic potentials evoked by stimulation of α1-adrenergic receptors located on local interneurons.",
keywords = "Interneuron, Noradrenalin, Phenylephrine, Potasium current, Substantia nigra, Ventral tegmental area",
author = "J. Grenhoff and North, {H. A.} and Steven Johnson",
year = "1995",
doi = "10.1111/j.1460-9568.1995.tb00692.x",
language = "English (US)",
volume = "7",
pages = "1707--1713",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Alpha1-adrenergic effects on dopamine neurons recorded intracellularly in the rat midbrain slice

AU - Grenhoff, J.

AU - North, H. A.

AU - Johnson, Steven

PY - 1995

Y1 - 1995

N2 - Previous studies have indicated excitatory adrenergic effects on midbrain dopamine systems. To investigate the cellular mechanisms, intracellular recordings were made from neurons in perfused, oxygenated slices of male rat midbrain. Electrophysiological and pharmacological parameters were used to identify cells as principal (presumably dopaminergic) neurons as opposed to secondary (presumably GABAergic) neurons in the substantia nigra zona compacta and the ventral tegmental area. Noradrenalin (10-100 μM) hyperpolarized 57% of all principal cells and depolarized 36%. Sulpiride (100-1000 nM), a dopamine D2 receptor antagonist, completely blocked noradrenalin-induced hyperpolarizations (six of six cells). In sulpiride, noradrenalin depolarized 58% of all principal neurons and had no effect in 42%; this effect was mimicked by the α-adrenergic agonist phenylephrine (10-30 μM) which depolarized 43 of 72 cells. The α1 receptor antagonist prazosin (30-100 nM) completely blocked the membrane depolarization produced by either noradrenalin or phenylephrine in all cells tested, whereas α2- and β-adrenergic agents had no effect. In voltage clamp, phenylephrine evoked an inward current (at -60 mV) and reduced cord conductance by 0.81 ± 0.14 nS (n = 4). Inward current evoked by phenylephrine became outward at -96 ± 8 mV, which is near the membrane reversal potential for potassium as predicted by the Nernst equation. Phenylephrine also depolarized secondary cells and increased the frequency of spontaneous GABA(A) receptor-mediated postsynaptic potentials recorded in both principal and secondary cells. We conclude that stimulation of α1-adrenergic receptors depolarizes principal (dopamine) neurons by reducing membrane conductance for potassium, but this effect is modulated by the increase in frequency of spontaneous inhibitory postsynpatic potentials evoked by stimulation of α1-adrenergic receptors located on local interneurons.

AB - Previous studies have indicated excitatory adrenergic effects on midbrain dopamine systems. To investigate the cellular mechanisms, intracellular recordings were made from neurons in perfused, oxygenated slices of male rat midbrain. Electrophysiological and pharmacological parameters were used to identify cells as principal (presumably dopaminergic) neurons as opposed to secondary (presumably GABAergic) neurons in the substantia nigra zona compacta and the ventral tegmental area. Noradrenalin (10-100 μM) hyperpolarized 57% of all principal cells and depolarized 36%. Sulpiride (100-1000 nM), a dopamine D2 receptor antagonist, completely blocked noradrenalin-induced hyperpolarizations (six of six cells). In sulpiride, noradrenalin depolarized 58% of all principal neurons and had no effect in 42%; this effect was mimicked by the α-adrenergic agonist phenylephrine (10-30 μM) which depolarized 43 of 72 cells. The α1 receptor antagonist prazosin (30-100 nM) completely blocked the membrane depolarization produced by either noradrenalin or phenylephrine in all cells tested, whereas α2- and β-adrenergic agents had no effect. In voltage clamp, phenylephrine evoked an inward current (at -60 mV) and reduced cord conductance by 0.81 ± 0.14 nS (n = 4). Inward current evoked by phenylephrine became outward at -96 ± 8 mV, which is near the membrane reversal potential for potassium as predicted by the Nernst equation. Phenylephrine also depolarized secondary cells and increased the frequency of spontaneous GABA(A) receptor-mediated postsynaptic potentials recorded in both principal and secondary cells. We conclude that stimulation of α1-adrenergic receptors depolarizes principal (dopamine) neurons by reducing membrane conductance for potassium, but this effect is modulated by the increase in frequency of spontaneous inhibitory postsynpatic potentials evoked by stimulation of α1-adrenergic receptors located on local interneurons.

KW - Interneuron

KW - Noradrenalin

KW - Phenylephrine

KW - Potasium current

KW - Substantia nigra

KW - Ventral tegmental area

UR - http://www.scopus.com/inward/record.url?scp=0028982998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028982998&partnerID=8YFLogxK

U2 - 10.1111/j.1460-9568.1995.tb00692.x

DO - 10.1111/j.1460-9568.1995.tb00692.x

M3 - Article

VL - 7

SP - 1707

EP - 1713

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 8

ER -