Hayar A, Feltz P, Piguet P
Laboratoire de Physiologie Générale, URA CNRS 1446, Université Louis Pasteur, Strasbourg, France.
Neuroscience. 1997 Mar;77(1):199-217. doi: 10.1016/s0306-4522(96)00445-9.
Noradrenaline and adrenergic agonists were tested on pacemaker-like and silent neurons of the rat rostral ventrolateral medulla using intracellular recording in coronal brainstem slices as well as in punches containing only the rostral ventrolateral medullary region. Noradrenaline (1-100 microM) depolarized or increased the frequency of discharge of all cells tested in a dose-dependent manner. The noradrenaline-induced depolarization was associated with an apparent increase in cell input resistance at low concentrations and a decrease or no significant change at higher concentrations. Moreover, it was voltage dependent and its amplitude decreased with membrane potential hyperpolarization. Noradrenaline caused a dose-related increase in the frequency and amplitude of spontaneous inhibitory postsynaptic potentials. The alpha 1-adrenoceptor antagonist prazosin (0.5 microM) abolished the noradrenaline depolarizing response as well as-the noradrenaline-evoked increase in synaptic activity and unmasked an underlying noradrenaline dose-dependent hyperpolarizing response associated with a decrease in cell input resistance and sensitive to the alpha 2-adrenoceptor/antagonist yohimbine (0.5 microM). The alpha 1-adrenoceptor agonist phenylephrine (10 microM) mimicked the noradrenaline depolarizing response associated with an increase in membrane resistance as well as the noradrenaline-induced increase in synaptic activity. The alpha 2-adrenoceptor agonists UK-14,304 (1-3 microM) and clonidine (10-30 microM) produced only a small hyperpolarizing response, whereas the beta-adrenoceptor agonist isoproterenol (10-30 microM) had no effect. Baseline spontaneous postsynaptic potentials were abolished by strychnine (1 microM), bicuculline (30 microM) or both. However, only the strychnine-sensitive postsynaptic potentials had their frequency increased by noradrenaline or phenylephrine and they usually occurred with a regular pattern. Tetrodotoxin (1 microM) eliminated 80-95% of baseline spontaneous postsynaptic potentials and prevented the increase in synaptic activity evoked by noradrenaline and phenylephrine. Similar results were obtained in rostral ventrolateral medulla neurons impaled in both coronal slices and punches of the rostral ventrolateral medulla. It is concluded that noradrenaline could play an important inhibitory role in the rostral ventrolateral medulla via at least two mechanisms: an alpha 2-adrenoceptor-mediated hyperpolarization and an enhancement of inhibitory synaptic transmission through activation of alpha 1-adrenoceptors located on the somatic membrane of glycinergic interneurons. Some of these interneurons exhibit a regular discharge similar to the pacemaker-like neurons and might, at least in part, constitute a central inhibitory link in the baroreceptor-vasomotor reflex pathway.
使用冠状脑干切片以及仅包含延髓头端腹外侧区域的组织块进行细胞内记录，对大鼠延髓头端腹外侧的起搏器样神经元和沉默神经元进行了去甲肾上腺素和肾上腺素能激动剂测试。去甲肾上腺素（1 - 100微摩尔）以剂量依赖性方式使所有测试细胞去极化或增加放电频率。低浓度时，去甲肾上腺素诱导的去极化与细胞输入电阻明显增加相关，而高浓度时则降低或无显著变化。此外，它具有电压依赖性，其幅度随膜电位超极化而降低。去甲肾上腺素使自发性抑制性突触后电位的频率和幅度呈剂量相关增加。α1肾上腺素能受体拮抗剂哌唑嗪（0.5微摩尔）消除了去甲肾上腺素的去极化反应以及去甲肾上腺素诱发的突触活动增加，并揭示了一种潜在的与细胞输入电阻降低相关且对α2肾上腺素能受体/拮抗剂育亨宾（0.5微摩尔）敏感的去甲肾上腺素剂量依赖性超极化反应。α1肾上腺素能受体激动剂去氧肾上腺素（10微摩尔）模拟了与膜电阻增加相关的去甲肾上腺素去极化反应以及去甲肾上腺素诱导的突触活动增加。α2肾上腺素能受体激动剂UK - 14,304（1 - 3微摩尔）和可乐定（10 - 30微摩尔）仅产生轻微的超极化反应，而β肾上腺素能受体激动剂异丙肾上腺素（10 - 30微摩尔）则无作用。士的宁（1微摩尔）、荷包牡丹碱（30微摩尔）或两者均可消除基线自发性突触后电位。然而，只有对士的宁敏感的突触后电位其频率会被去甲肾上腺素或去氧肾上腺素增加，且它们通常以规则模式出现。河豚毒素（1微摩尔）消除了80 - 95%的基线自发性突触后电位，并阻止了去甲肾上腺素和去氧肾上腺素诱发的突触活动增加。在冠状切片和延髓头端腹外侧组织块中刺入的延髓头端腹外侧神经元中获得了类似结果。得出的结论是，去甲肾上腺素可能通过至少两种机制在延髓头端腹外侧发挥重要的抑制作用：α2肾上腺素能受体介导的超极化以及通过激活甘氨酸能中间神经元体膜上的α1肾上腺素能受体增强抑制性突触传递。其中一些中间神经元表现出类似于起搏器样神经元的规则放电，并且可能至少部分构成压力感受器 - 血管运动反射途径中的中枢抑制环节。
