Jiang Zhenglin, Krnjević Kresimir, Wang Fushun, Ye Jiang Hong
Departments of Anesthesiology, Pharmacology, and Physiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103-2714, USA.
J Neurophysiol. 2004 Jan;91(1):248-57. doi: 10.1152/jn.00106.2003. Epub 2003 Jul 23.
Although functional glycine receptors (GlyRs) are present in the mature nucleus accumbens (NAcc), an important area of the mesolimbic dopamine system involved in drug addiction, their role has been unclear because the NAcc contains little glycine. However, taurine, an agonist of GlyRs, is abundant throughout the brain, especially during early development. In the present study on freshly dissociated NAcc neurons from young Sprague-Dawley rats (12- to 21-day old), we found that both glycine and taurine can strongly depolarize NAcc neurons and modulate their excitability. In voltage-clamped NAcc neurons, glycine and taurine elicited chloride currents (IGly and ITau) with an EC50 of 0.12 and 1.25 mM, respectively. The reversal potential of IGly or ITau was 0 mV in conventional whole cell mode and -30 mV in gramicidin-perforated mode. At concentrations <1 mM, both glycine and taurine were very effectively antagonized by strychnine and by picrotoxin (with an IC50 of 60 nM and 36.5 microM for IGly, and 40 nM and 42.2 microM for ITau) but were insensitive to 10 microM bicuculline. The currents elicited by taurine (< or =1 mM) showed complete cross-desensitization with IGly, but none with gamma-aminobutyric acid (GABA)-induced currents (IGABA). However, ITau elicited by very concentrated taurine (10 mM) showed partial cross-desensitization with IGABA, and it was substantially antagonized by 10 microM bicuculline. These results indicate that taurine binds mainly to GlyRs in NAcc, but it could be a partial agonist of GABAA receptors. By activating GlyRs, taurine may play an important physiological role in the control of NAcc function, especially during development.
尽管功能性甘氨酸受体(GlyRs)存在于成熟的伏隔核(NAcc)中,伏隔核是中脑边缘多巴胺系统中参与药物成瘾的一个重要区域,但其作用一直不明确,因为伏隔核中甘氨酸含量很少。然而,牛磺酸作为GlyRs的一种激动剂,在整个大脑中含量丰富,尤其是在早期发育阶段。在本研究中,我们使用来自幼年Sprague-Dawley大鼠(12至21日龄)新鲜分离的伏隔核神经元,发现甘氨酸和牛磺酸均可使伏隔核神经元强烈去极化并调节其兴奋性。在电压钳制的伏隔核神经元中,甘氨酸和牛磺酸分别以0.12 mM和1.25 mM的半数有效浓度(EC50)引发氯离子电流(IGly和ITau)。在传统全细胞模式下,IGly或ITau的反转电位为0 mV,在短杆菌肽穿孔模式下为 -30 mV。在浓度<1 mM时,甘氨酸和牛磺酸均能被士的宁和苦味毒非常有效地拮抗(IGly的半数抑制浓度(IC50)为60 nM和36.5 μM,ITau的IC50为40 nM和42.2 μM),但对10 μM荷包牡丹碱不敏感。牛磺酸(≤1 mM)引发的电流与IGly表现出完全交叉脱敏,但与γ-氨基丁酸(GABA)诱导的电流(IGABA)无交叉脱敏。然而,高浓度牛磺酸(10 mM)引发的ITau与IGABA表现出部分交叉脱敏,并且被10 μM荷包牡丹碱显著拮抗。这些结果表明,牛磺酸主要与伏隔核中的GlyRs结合,但它可能是GABAA受体的部分激动剂。通过激活GlyRs,牛磺酸可能在控制伏隔核功能中发挥重要的生理作用,尤其是在发育过程中。