Cui L N, Coderre E, Renaud L P
Laboratory of Neurosciences, Loeb Health Research Institute, Ottawa Hospital Civic Site; and University of Ottawa, Ottawa, Ontario, Canada K1Y 4E9.
Am J Physiol Regul Integr Comp Physiol. 2000 May;278(5):R1210-6. doi: 10.1152/ajpregu.2000.278.5.R1210.
This study used whole cell patch clamp recordings in rat hypothalamic slice preparations to evaluate the effects of GABA(B) receptor activation on GABA(A)-mediated inhibitory postsynaptic currents (IPSCs) in paraventricular nucleus magnocellular neurons evoked by electrical stimulation in the suprachiasmatic nucleus (SCN). Baclofen induced a dose-dependent (1-10 microM) and reversible reduction in SCN-evoked IPSC amplitude (11/11 cells), blockable with 2-hydroxysaclofen (300 microM; 3/3 cells). IPSCs displayed paired-pulse depression (PPD), attenuated by both baclofen and 2-hydroxysaclofen, but neither altered resting membrane conductances or IPSC time constants of decay. Baclofen induced a significant dose-dependent (1-100 microM) reduction in frequency, but not amplitude, of spontaneous IPSCs and miniature IPSCs, reversible with 2-hydroxysaclofen pretreatment. Baclofen effects and PPD persisted in slices pretreated with pertussis toxin (PTX) and N-ethylmaleimide, implying that these GABA(B) receptors are coupled to PTX-insensitive G proteins. Responses were unaltered by barium (2 mM) or nimodipine, ruling out involvement of K(+) channels and L-type Ca(2+) channels. Thus pre- and postsynaptic GABA(B) and GABA(A) receptors participate in SCN entrainment of paraventricular neurosecretory neurons.
本研究采用大鼠下丘脑脑片制备中的全细胞膜片钳记录技术，以评估GABA(B)受体激活对在视交叉上核（SCN）进行电刺激诱发的室旁核大细胞神经元中GABA(A)介导的抑制性突触后电流（IPSCs）的影响。巴氯芬可剂量依赖性（1 - 10 microM）且可逆地降低SCN诱发的IPSC幅度（11/11个细胞），2 - 羟基巴氯芬（300 microM；3/3个细胞）可阻断该作用。IPSCs表现出双脉冲抑制（PPD），巴氯芬和2 - 羟基巴氯芬均可使其减弱，但二者均未改变静息膜电导或IPSC的衰减时间常数。巴氯芬可剂量依赖性（1 - 100 microM）地显著降低自发性IPSCs和微小IPSCs的频率，但不改变其幅度，用2 - 羟基巴氯芬预处理可使其作用逆转。在经百日咳毒素（PTX）和N - 乙基马来酰亚胺预处理的脑片中，巴氯芬的作用及PPD仍然存在，这表明这些GABA(B)受体与对PTX不敏感的G蛋白偶联。钡（2 mM）或尼莫地平对反应无影响，排除了K(+)通道和L型Ca(2+)通道的参与。因此，突触前和突触后的GABA(B)及GABA(A)受体参与了视交叉上核对室旁神经分泌神经元的同步化过程。
