Hernández-López S, Bargas J, Surmeier D J, Reyes A, Galarraga E
Departamento de Biofísica, Instituto de Fisiología Celular, Universidad Nacional Autonoma de Mexico, México City DF, 04510 México.
J Neurosci. 1997 May 1;17(9):3334-42. doi: 10.1523/JNEUROSCI.17-09-03334.1997.
Most in vitro studies of D1 dopaminergic modulation of excitability in neostriatal medium spiny neurons have revealed inhibitory effects. Yet studies made in more intact preparations have shown that D1 receptors can enhance or inhibit the responses to excitatory stimuli. One explanation for these differences is that the effects of D1 receptors on excitability are dependent on changes in the membrane potential occurring in response to cortical inputs that are seen only in intact preparations. To test this hypothesis, we obtained voltage recordings from medium spiny neurons in slices and examined the impact of D1 receptor stimulation at depolarized and hyperpolarized membrane potentials. As previously reported, evoked discharge was inhibited by D1 agonists when holding at negative membrane potentials (approximately -80 mV). However, at more depolarized potentials (approximately -55 mV), D1 agonists enhanced evoked activity. At these potentials, D1 agonists or cAMP analogs prolonged or induced slow subthreshold depolarizations and increased the duration of barium- or TEA-induced Ca2+-dependent action potentials. Both effects were blocked by L-type Ca2+ channel antagonists (nicardipine, calciseptine) and were occluded by the L-type channel agonist BayK 8644-arguing that the D1 receptor-mediated effects on evoked activity at depolarized membrane potential were mediated by enhancement of L-type Ca2+ currents. These results reconcile previous in vitro and in vivo studies by showing that D1 dopamine receptor activation can either inhibit or enhance evoked activity, depending on the level of membrane depolarization.
大多数关于新纹状体中等棘状神经元中D1多巴胺能对兴奋性调节的体外研究都揭示了其抑制作用。然而，在更完整的标本上进行的研究表明，D1受体可以增强或抑制对兴奋性刺激的反应。对这些差异的一种解释是，D1受体对兴奋性的影响取决于膜电位的变化，而这种变化是对仅在完整标本中可见的皮质输入做出的反应。为了验证这一假设，我们从脑片中的中等棘状神经元获得了电压记录，并研究了在去极化和超极化膜电位下D1受体刺激的影响。如先前报道，当保持在负膜电位（约-80 mV）时，D1激动剂抑制诱发放电。然而，在更去极化的电位（约-55 mV）下，D1激动剂增强了诱发活动。在这些电位下，D1激动剂或cAMP类似物延长或诱导了缓慢的阈下去极化，并增加了钡或TEA诱导的Ca2+依赖性动作电位的持续时间。这两种效应均被L型Ca2+通道拮抗剂（尼卡地平、钙阻滞剂）阻断，并被L型通道激动剂BayK 8644阻断——这表明D1受体介导的在去极化膜电位下对诱发活动的影响是由L型Ca2+电流增强介导的。这些结果通过表明D1多巴胺受体激活可以根据膜去极化水平抑制或增强诱发活动来调和先前的体外和体内研究。
