ALPHA(1)-ADRENERGIC EFFECTS ON DOPAMINE NEURONS RECORDED INTRACELLULARLY IN THE RAT MIDBRAIN SLICE
ALPHA(1)-ADRENERGIC EFFECTS ON DOPAMINE NEURONS RECORDED INTRACELLULARLY IN THE RAT MIDBRAIN SLICE
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DOI：
10.1111/j.1460-9568.1995.tb00692.x
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发表时间：
1995-08-01
影响因子：
3.4
通讯作者：
JOHNSON, SW
中科院分区：
文献类型：
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作者：
GRENHOFF, J;NORTH, RA;JOHNSON, SW
先前的研究表明兴奋性肾上腺素能作用于中脑多巴胺系统。为了研究细胞机制，我们对雄性大鼠中脑灌注充氧切片的神经元进行了细胞内记录。使用电生理和药理学参数来识别黑质致密带和腹侧被盖区的主要（可能是多巴胺能）神经元和次要（可能是gaba能）神经元。去甲肾上腺素（10-100 μ M）使57%的主细胞超极化，36%的主细胞去极化。舒必利（100-1000 nM），一种多巴胺D-2受体拮抗剂，完全阻断去甲肾上腺素诱导的超极化（6个细胞中的6个），在舒必利中，去甲肾上腺素去极化58%的主要神经元，42%的主要神经元没有影响；肾上腺素能激动剂苯肾上腺素（10-30 μ M）能模拟这种效应，使72个细胞中的43个去极化。α(1)受体拮抗剂prazosin （30-100 nM）完全阻断了所有细胞中由去甲肾上腺素或苯肾上腺素产生的膜去极化，而α(2)和β肾上腺素能药物没有作用。在电压箝位中，苯肾上腺素引起向内电流（-60 mV），使脐带电导降低0.81±0.14 nS （n = 4）。苯肾上腺素引起的内向电流在-96 +/- 8 mV时向外转变，接近能斯特方程预测的钾的膜反转电位。苯肾上腺素还能使次级细胞去极化，并增加主细胞和次级细胞中自发性GABA(A)受体介导的突触后电位的频率。我们得出的结论是，刺激α(1)-肾上腺素能受体通过降低钾的膜电导使主要（多巴胺）神经元去极化，但这种作用是通过刺激位于局部中间神经元的α(1)-肾上腺素能受体引起的自发抑制性突触后电位频率的增加来调节的。
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 mu M) hyperpolarized 57% of all principal cells and depolarized 36%. Sulpiride (100-1000 nM), a dopamine D-2 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 alpha-adrenergic agonist phenylephrine (10-30 mu M) which depolarized 43 of 72 cells. The alpha(1) receptor antagonist prazosin (30-100 nM) completely blocked the membrane depolarization produced by either noradrenalin or phenylephrine in all cells tested, whereas alpha(2)- and beta-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 alpha(1)-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 postsynaptic potentials evoked by stimulation of alpha(1)-adrenergic receptors located on local interneurons.