Earnest D J, Digiorgio S M, Sladek C D
University of Rochester Medical Center, Department of Neurobiology/Anatomy, NY 14642.
Brain Res Bull. 1991 May;26(5):677-82. doi: 10.1016/0361-9230(91)90160-l.
Using perifused explants of the rat suprachiasmatic nucleus (SCN), the effects of tetrodotoxin (TTX) on vasopressin (VP) release and its circadian profile were studied at various times throughout the circadian cycle. VP release from SCN explants was consistently attenuated during TTX treatment, with the amplitude of this effect depending on the time of administration. In addition, the effect of TTX on the circadian pattern of VP release was also time-dependent, such that treatment during the late subjective day was followed by a disruption of circadian rhythmicity in which peptide output remained at basal levels without notable variation whereas treatment at all other times caused no measurable perturbation in the circadian VP rhythm in succeeding cycles. In SCN explants experiencing this TTX-induced arrest of circadian VP output, subsequent exposure to KCl induced acute increases in VP release, suggesting that VP neurons retain the capacity to actively release peptide in spite of this effect of TTX. These results indicate that the interruption of electrical impulses at a critical phase may compromise the circadian function or output of the pacemaker in the SCN. In addition, the present observations provide further evidence that the overt expression of circadian rhythmicity is dependent on sodium-generated action potentials and that disruption of these electrical signals does not alter the precision of the SCN pacemaker, at least in instances where the phase of the VP rhythm can be determined after treatment.
利用大鼠视交叉上核（SCN）的灌流外植体，在昼夜节律周期的不同时间研究了河豚毒素（TTX）对血管加压素（VP）释放及其昼夜节律的影响。在TTX处理期间，SCN外植体的VP释放持续减弱，这种效应的幅度取决于给药时间。此外，TTX对VP释放昼夜模式的影响也具有时间依赖性，因此在主观日后期进行处理后，昼夜节律会被破坏，其中肽输出保持在基础水平且无明显变化，而在其他所有时间进行处理在后续周期中不会对昼夜VP节律造成可测量的干扰。在经历这种TTX诱导的昼夜VP输出停滞的SCN外植体中，随后暴露于KCl会导致VP释放急性增加，这表明尽管有TTX的这种作用，VP神经元仍保留主动释放肽的能力。这些结果表明，在关键阶段电冲动的中断可能会损害SCN中起搏器的昼夜功能或输出。此外，目前的观察结果提供了进一步的证据，即昼夜节律的明显表达依赖于钠产生的动作电位，并且这些电信号的中断不会改变SCN起搏器的精度，至少在治疗后可以确定VP节律相位的情况下是如此。
