Intracellular chloride modulates A-type potassium currents in astrocytes
Intracellular chloride modulates A-type potassium currents in astrocytes
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作者：
Bekar, LK;Walz, W
将GABA（A）受体激动剂蝇蕈醇应用于原位或体外星形胶质细胞导致受体介导的Cl-电流，同时阻断外向K+电流。对K+电流的影响在很大程度上是选择性的失活A型电流。不同Cl-移液管浓度的平行实验表明，在低Cl-条件下，A型电流显着减少，对延迟电流的影响最小。此外，较低的Cl-条件仅导致A型电流的稳态失活（V-1/2，-68至-57 mV）和激活（V-1/2，-5.5至34 mV）动力学的去极化偏移。Cl-对失活或再活化动力学的时间过程没有影响，表明Cl-介导的影响主要是在活化动力学上，间接影响稳态失活。蝇蕈醇应用于星形胶质细胞穿孔补丁控制（短杆菌肽）显示出类似的块A型电流的传统的全细胞补丁在40或20 mM的移液管Cl-浓度。在穿孔贴片条件下应用钡，研究蝇蕈醇介导的Cl-电流对K+电流的影响是可能的。这允许从受体电流逆转信息估计细胞内Cl-浓度。发现平均细胞内Cl-浓度为29 +/- 3.2 mM。对激活动力学的影响和对失活或再激活的时间过程缺乏影响表明细胞内阴离子浓度对K+通道电压传感器区域有影响。Cl-可通过改变K+通道蛋白周围的膜场电位来调节K+电流。
Application of the GABA(A) receptor agonist muscimol to astrocytes in situ or in vitro results in a receptor-mediated Cl- current with a concomitant block of outward K+ currents. The effect on K+ current is largely selective for the inactivating A-type current. Parallel experiments with various Cl- pipette concentrations show a significant reduction in A-type current under low Cl- conditions with minimal effect on delayed current. In addition, lower Cl- conditions caused a depolarizing shift of steady-state inactivation (V-1/2, -68 to -57 mV) and activation (V-1/2, -5.S to 34 mV) kinetics of A-type current only. Cl- had no effect on the time course of inactivation or reactivation kinetics, suggesting the Cl--mediated effect is largely on activation kinetics, indirectly affecting steady-state inactivation. Muscimol application to astrocytes under perforated patch control (gramicidin) displayed a similar block of A-type current to that of conventional whole cell patch at 40 or 20 mM pipette Cl- concentrations. With barium application under perforated patch conditions, the study of muscimol-mediated Cl- current in isolation of the effect on K+ currents was possible. This allowed estimation of intracellular Cl- concentration from receptor current reversal information. The average intracellular Cl- concentration was found to be 29 +/- 3.2 mM. The effect on activation kinetics and lack of effect on time course of inactivation or reactivation suggest that intracellular anion concentrations have an effect on the K+ channel voltage sensor region. Cl- may modulate K+ currents by altering membrane field potentials surrounding K+ channel proteins.