Surprenant A, Crist J
Neuropharmacology Laboratory, Massachusetts Institute of Technology, Cambridge 02139.
Neuroscience. 1988 Jan;24(1):283-95. doi: 10.1016/0306-4522(88)90331-4.
Intracellular recordings were made from neurons of the guinea-pig submucous plexus and the actions of 5-hydroxytryptamine on the postsynaptic membrane and on evoked synaptic potentials were examined. 5-Hydroxytryptamine produced two types of direct postsynaptic responses: (1) A depolarization associated with a fall in input resistance was observed in all cells. Voltage-clamp and ion substitutions showed that this depolarization resulted primarily from an inward sodium current. This response could be as brief as 30 ms; it showed desensitization and was selectively abolished by 0.2-2 microM ICS 205-930. (2) A depolarization (or inward current) associated with a decreased conductance was observed in about 50% of neurons, usually after the first response was blocked by ICS 205-930. This response was due to a decreased potassium conductance; the minimum time course of this response was 8-10 s. It did not show desensitization and was not sensitive to blockade by currently available antagonists of 5-hydroxytryptamine, nicotinic and/or muscarinic receptors. Higher concentrations of 5-hydroxytryptamine were required to produce the sodium conductance increase than the potassium conductance decrease; 2-methyl-5-hydroxytryptamine was equally effective in producing these responses. 5-Hydroxytryptamine also caused a barrage of "spontaneous" nicotinic excitatory post-synaptic potentials which were sensitive to tetrodotoxin. This response desensitized, was blocked by ICS 205-930 and is presumed to reflect excitation of other cholinergic cell bodies in the plexus by the sodium conductance increase mechanism described. The evoked nicotinic excitatory postsynaptic potential and the adrenergic inhibitory postsynaptic potential were decreased by 5-hydroxytryptamine; a portion of this inhibition showed desensitization and was blocked by ICS 205-930 as well as by the muscarinic receptor antagonists, atropine and pirenzepine. The ICS 205-930-insensitive portion of this inhibition could not be attributed to activation of 5-hydroxytryptamine-1 or 5-hydroxytryptamine-2 receptors. Thus, the following conclusions are drawn: 5-hydroxytryptamine excites submucous plexus neurons by activating two distinct 5-hydroxytryptamine receptors. Activation of the 5-hydroxytryptamine-3 receptor (sensitive to ICS 205-930) produces a depolarization mediated by an increased sodium conductance. The same effect occurring in other cholinergic cell bodies initiates action potentials which are responsible for the 5-hydroxytryptamine-induced release of acetylcholine.(ABSTRACT TRUNCATED AT 400 WORDS)
对豚鼠黏膜下神经丛的神经元进行细胞内记录，并研究了5-羟色胺对突触后膜和诱发突触电位的作用。5-羟色胺产生两种类型的直接突触后反应：（1）在所有细胞中均观察到与输入电阻下降相关的去极化。电压钳和离子置换表明，这种去极化主要由内向钠电流引起。这种反应可能短至30毫秒；它表现出脱敏作用，并被0.2 - 2微摩尔的ICS 205 - 930选择性消除。（2）在约50%的神经元中观察到与电导降低相关的去极化（或内向电流），通常在ICS 205 - 930阻断第一个反应之后出现。这种反应是由于钾电导降低；该反应的最短时程为8 - 10秒。它不表现出脱敏作用，并且对目前可用的5-羟色胺、烟碱和/或毒蕈碱受体拮抗剂的阻断不敏感。产生钠电导增加所需的5-羟色胺浓度高于钾电导降低所需的浓度；2-甲基-5-羟色胺在产生这些反应方面同样有效。5-羟色胺还引起一连串对河豚毒素敏感的“自发性”烟碱兴奋性突触后电位。这种反应会脱敏，被ICS 205 - 930阻断，推测是通过上述钠电导增加机制反映了神经丛中其他胆碱能细胞体的兴奋。5-羟色胺使诱发的烟碱兴奋性突触后电位和肾上腺素能抑制性突触后电位降低；这种抑制作用部分表现出脱敏作用，并被ICS 205 - 930以及毒蕈碱受体拮抗剂阿托品和哌仑西平阻断。这种抑制作用中对ICS 205 - 930不敏感的部分不能归因于5-羟色胺-1或5-羟色胺-2受体的激活。因此，得出以下结论：5-羟色胺通过激活两种不同的5-羟色胺受体来兴奋黏膜下神经丛神经元。5-羟色胺-3受体（对ICS 205 - 930敏感）的激活产生由钠电导增加介导的去极化。在其他胆碱能细胞体中发生的相同效应引发动作电位，这些动作电位负责5-羟色胺诱导的乙酰胆碱释放。（摘要截短于400字）
