Chen Hsin-Kai, Su Chun-Kuei
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
Neuropharmacology. 2006 Dec;51(7-8):1120-8. doi: 10.1016/j.neuropharm.2006.06.015. Epub 2006 Aug 10.
Without the brainstem, thoracic spinal cords of neonatal rats in vitro spontaneously generate tonic sympathetic nerve discharge (SND) in the splanchnic nerves. Activation of nicotinic receptors in cords is known to alter a repertoire of neurotransmitter releases to sympathetic preganglionic neurons (SPNs). Using in vitro nerve-cord preparations, we investigated whether endogenous nicotinic receptor activity is essential for SND genesis. Application of mecamylamine, an open-channel nicotinic receptor blocker, reduced SND in a progressive manner. Exogenous activation of nicotinic receptors by application of various nicotinic agonists generally excited SND at low agonistic concentrations. At higher concentrations, however, agonists induced biphasic responses characterized by an initial excitation followed by prolonged SND suppression. Whether ionotropic glutamate, GABA(A), or glycine receptors are downstream signals of nicotinic receptor activation was explored by pretreatment of cords with selective antagonists. The initial excitation of SND persisted in the presence of ionotropic glutamate receptor antagonists. In contrast, the SND suppression was partially reversed by glycine or GABA(A) receptor antagonists. Incubation of the cord in a low Ca(2+)/high Mg(2+) bath solution to block Ca(2+)-dependent synaptic transmission did not affect SND excitation induced by nicotinic agonists, confirming direct activation of postsynaptic nicotinic receptors on SPNs. In conclusion, the endogenous activity of nicotinic receptors is essential for SND genesis in the thoracic spinal cord. Nicotinic activation of glycinergic and GABAergic interneurons may provide a recurrent inhibition of SPNs for homeostatic regulation of sympathetic outflow.
没有脑干的情况下，新生大鼠的胸段脊髓在体外可自发产生内脏神经中的紧张性交感神经放电（SND）。已知脊髓中烟碱样受体的激活会改变向交感神经节前神经元（SPN）释放的一系列神经递质。我们使用体外神经-脊髓制备物，研究内源性烟碱样受体活性对于SND产生是否必不可少。应用开放通道烟碱样受体阻滞剂美加明可逐渐降低SND。通过应用各种烟碱样激动剂对外源性激活烟碱样受体，在低激动剂浓度下通常会兴奋SND。然而，在较高浓度下，激动剂会诱导双相反应，其特征是最初兴奋，随后是SND长期抑制。通过用选择性拮抗剂预处理脊髓，探究离子型谷氨酸、GABAA或甘氨酸受体是否为烟碱样受体激活的下游信号。在离子型谷氨酸受体拮抗剂存在的情况下，SND的最初兴奋持续存在。相反，甘氨酸或GABAA受体拮抗剂可部分逆转SND抑制。将脊髓置于低钙/高镁浴液中孵育以阻断钙依赖性突触传递，并不影响烟碱样激动剂诱导的SND兴奋，证实了SPN上突触后烟碱样受体的直接激活。总之，烟碱样受体的内源性活性对于胸段脊髓中SND的产生至关重要。烟碱样激活甘氨酸能和GABA能中间神经元可能为SPN提供反复抑制，以实现交感神经输出的稳态调节。
