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血管加压素诱导的新生大鼠脊髓外侧角神经元电流由G蛋白介导,并涉及两种电导。

Vasopressin-induced currents in rat neonatal spinal lateral horn neurons are G-protein mediated and involve two conductances.

作者信息

Kolaj M, Renaud L P

机构信息

Neuroscience, Loeb Research Institute, Ottawa Civic Hospital and University of Ottawa, Ottawa, Ontario K1Y 4E9, Canada.

出版信息

J Neurophysiol. 1998 Oct;80(4):1900-10. doi: 10.1152/jn.1998.80.4.1900.

Abstract

Arginine vasopressin (AVP) receptors are expressed early in the developing spinal cord. To characterize AVP-induced conductances in lower thoracic sympathetic preganglionic (SPN) and other lateral horn neurons, we used patch-clamp recording techniques in neonatal (11-21 days) rat spinal cord slices. Most (90%) of 273 neurons, including all 68 SPNs, responded to AVP with membrane depolarization and/or a V1 receptor-mediated, dose-dependent (0.01-1.0 microM) and tetrodotoxin (TTX)-resistant inward current. A role for G-proteins was indicated by persistence of this inward current after intracellular dialysis with GTP-gamma-S or GMP-PNP, its marked reduction with GDP-beta-S, and significant reduction, but not abolition, after preincubation with pertussis toxin or in the presence of N-ethylmaleimide. Analysis of individual current-voltage (I-V) relationships in 57 cells indicated the presence of two different membrane conductances. In 21 cells, net AVP-induced currents reversed around -103 mV, reflecting reduction in one or more barium-sensitive potassium conductances; in 12 cells, net AVP-induced current reversed around -40 mV and was not significantly sensitive to several potassium channel blockers including barium, tetraethylammonium chloride (TEA), 4-aminopyridine (4AP), cesium, or glibenclamide, suggesting increase in a nonselective cationic conductance that was separate from Ih; in 24 cells where I-V lines shifted in parallel, AVP-induced inward currents were significantly greater and probably involved both conductances. These data indicate that SPNs and a majority of unidentified neonatal lateral horn neurons possess functional G-protein-coupled V1-type vasopressin receptors. The wide distribution of AVP receptors in neonatal spinal lateral column cells suggests a role that may extend beyond involvement in regulation of autonomic nervous system function.

摘要

精氨酸加压素(AVP)受体在脊髓发育早期就有表达。为了描述AVP在下胸段交感神经节前(SPN)和其他外侧角神经元中诱导的电导,我们在新生(11 - 21天)大鼠脊髓切片中使用了膜片钳记录技术。273个神经元中的大多数(90%),包括所有68个SPN,对AVP产生膜去极化反应和/或一种V1受体介导的、剂量依赖性(0.01 - 1.0 microM)且对河豚毒素(TTX)不敏感的内向电流。在用GTP - γ - S或GMP - PNP进行细胞内透析后,这种内向电流持续存在,用GDP - β - S处理后显著降低,在用百日咳毒素预孵育后或在N - 乙基马来酰亚胺存在的情况下显著降低但未消除,这表明G蛋白起了作用。对57个细胞的单个电流 - 电压(I - V)关系分析表明存在两种不同的膜电导。在21个细胞中,净AVP诱导电流在约 - 103 mV处反转,反映出一种或多种钡敏感钾电导降低;在12个细胞中,净AVP诱导电流在约 - 40 mV处反转,并且对包括钡、氯化四乙铵(TEA)、4 - 氨基吡啶(4AP)、铯或格列本脲在内的几种钾通道阻滞剂不敏感,这表明一种与Ih不同的非选择性阳离子电导增加;在I - V线平行移动的24个细胞中,AVP诱导的内向电流显著更大,可能涉及两种电导。这些数据表明SPN和大多数未鉴定的新生外侧角神经元具有功能性G蛋白偶联的V1型加压素受体。AVP受体在新生脊髓外侧柱细胞中的广泛分布表明其作用可能超出了对自主神经系统功能调节的参与范围。

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