Ionic basis of the postsynaptic depolarizing GABA response in hippocampal pyramidal cells
Ionic basis of the postsynaptic depolarizing GABA response in hippocampal pyramidal cells
复制标题
DOI：
10.1152/jn.1996.76.6.3886
复制
发表时间：
1996-12-01
影响因子：
2.5
通讯作者：
Wong, RKS
中科院分区：
文献类型：
--
作者：
Perkins, KL;Wong, RKS
1. 采用不同离子组成的记录移液液进行全细胞电压钳记录，测定去极化γ -氨基丁酸（GABA）反应的离子基础。在4-氨基吡啶和兴奋性氨基酸受体阻滞剂存在的情况下，在成年豚鼠海马切片CA3锥体神经元中记录到了巨大的gaba介导的突触后电流（gpsc）。阻断GABA(B)组分后，GPSC由初始外向电流（GABA(A)组分）组成，其峰值为115 ms，随后是后期内向电流（GABA(D)组分），峰值为400-600 ms.2。细胞内钾离子（[K+](i)）浓度的降低没有导致GPSC中GABA(D)组分的逆转电位发生显著变化，表明它不是一个非特异性阳离子电流。通过记录含有三种不同浓度碳酸氢盐（[HCO3-]、19、49和102 mM）的移液管溶液，评估了介导GABA(D)反应的通道的HCO3-通透性。GABA的逆转电位，响应随着HCO3-平衡电位向去极化方向移动而向去极化方向移动，表明介导GABA响应的通道(D)对HCO3-是可渗透的。GABA的逆转电位，响应对记录移液器[HCO3-]的变化比GABA的逆转电位(A)，响应更敏感。说明GABA(D)反应在更大程度上是由HCO3-携带的，而不是GABA(a)反应。采用高[Cl-]/低[HCO3-]记录液（40 mM Cl-/6 mh3 HCO3-）将双相GPSC的外向-内向电流序列逆转为内向-外向电流序列。说明GABA组分对[Cl-](i)的变化更敏感，GABA(D)组分对[HCO3-](i)的变化更敏感。这些数据表明GPSC的GABA(D)组分主要由HCO3-携带。虽然这一结果支持最近提出的氯离子积累模型，但目前形式的模型不能解释细胞内高[Cl-]/低[HCO3-]溶液记录的GPSC的内向-外向电流极性序列。使用该溶液获得的数据表明，需要一个更广泛的氯化物积累/耗尽模型，或者使用具有不同阴离子渗透比的两种不同的异离子型GABA通道的模型，以解释GPSC的双相性质。
1. Whole cell voltage-clamp recording with recording pipette solutions of differing ionic composition was used to determine the ionic basis of the depolarizing gamma-aminobutyric acid (GABA) response. In the presence of 4-aminopyridine and excitatory amino acid receptor blockers, giant GABA-mediated postsynaptic currents (GPSCs) were recorded from CA3 pyramidal neurons in hippocampal slices from adult guinea pigs. With the GABA(B) component blocked, the GPSC was composed of an initial outward current (GABA(A) component) that peaked at 115 ms followed by a late inward current (GABA(D) component) that peaked at 400-600 ms.2. Reduction of the intracellular concentration of potassium ([K+](i))resulted in no significant change in the reversal potential of the GABA(D) component of the GPSC, indicating that it is not a nonspecific cation current.3. The HCO3- permeability of the channel mediating the GABA(D) response was assessed by using recording pipette solutions containing three different concentrations of bicarbonate ([HCO3-], 19, 49, and 102 mM). The reversal potential of the GABA, response shifted in the depolarizing direction as the HCO3- equilibrium potential was shifted in the depolarizing direction, indicating that the channel mediating the GABA(D) response is permeable to HCO3- The reversal potential of the GABA, response was more sensitive to changes in recording pipette [HCO3-] than the reversal potential of the GAB(A), response, indicating that the GABA(D) response is carried by HCO3- to a greater extent than the GABA(A) response.4. The outward current-inward current sequence of the biphasic GPSC was reversed to an inward current-outward current sequence by using a high [Cl-]/low [HCO3-] recording pipette solution (40 mM Cl-/6 mh3 HCO3-). indicating that the GABA, component is more sensitive to changes in [Cl-](i), and the GABA(D) component is more sensitive to changes in [HCO3-](i).5. These data indicate that the GABA(D) component of the GPSC is predominantly carried by HCO3-. While this result supports the recently proposed chloride accumulation model, the model in its present form cannot explain the inward current-outward current polarity sequence of the GPSC recorded with the high [Cl-]/low [HCO3-] intracellular solution. The data obtained using that solution reveal the need for a more expansive chloride accumulation/depletion model or for a model utilizing two distinct ionotropic GABA channels with different anion permeability ratios to account for the biphasic nature of the GPSC.