Voltage-dependent modulation of GABAA receptor channel desensitization in rat hippocampal neurons.
Voltage-dependent modulation of GABAA receptor channel desensitization in rat hippocampal neurons.
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大鼠海马神经元 GABAA 受体通道脱敏的电压依赖性调节。
DOI：
10.1152/jn.1994.71.6.2151
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发表时间：
1994
影响因子：
2.5
通讯作者：
Yoon,KW
中科院分区：
文献类型：
--
作者：
Yoon,KW
1.采用全细胞电压钳记录技术，在离体培养的大鼠海马细胞中研究了γ-氨基丁酸（GABA）诱导的氯离子电导随时间下降的机制。2.在大多数细胞中，膜电导的逐渐下降同时依赖于激动剂浓度和膜电压。即使在持续存在的GABA，脱敏可以防止保持膜电位> 0 mV，在一个接近对称的氯离子梯度跨细胞膜。3.脱敏的“恢复”发生在去除激动剂后，时间常数约为35 s。从脱敏的恢复率是独立的膜电压。4.当膜电位从负到正的膜电位在稳态的脱敏跳跃，GABA诱导的氯离子电导逐渐“放松”到非脱敏状态。这种氯离子电导逐渐增加的现象或从脱敏中“再激活”的现象是电压和激动剂依赖性的。5. GABA离子载体从脱敏状态恢复的过程不同于再激活的过程，其依赖于电压和激动剂。6.这些观察结果表明，配体结合的GABA受体具有两种交替状态，即，激活（activated）和脱敏。这两种状态之间的转换速率取决于电压。
1. The mechanism of the time-dependent decline in gamma-amino-butyric acid (GABA)-induced chloride conductance, referred to as desensitization, was studied in dissociated rat hippocampal cell culture with the use of a whole-cell voltage-clamp recording. 2. In most cells the gradual decline of membrane conductance was dependent simultaneously on the agonist concentration and membrane voltage. Even in the continued presence of GABA, desensitization could be prevented by holding the membrane potential > 0 mV in a near symmetrical chloride gradient across the cell membrane. 3. The “recovery” from desensitization occurred after removal of the agonist with a time constant of approximately 35 s. The rate of recovery from desensitization was independent of membrane voltage. 4. When the membrane potential was jumped from a negative to a positive membrane potential during steady state of desensitization, the GABA-induced chloride conductance gradually “relaxed” to the undesensitized state. This phenomenon of gradual increase in chloride conductance or “reactivation” from desensitization was both voltage and agonist dependent. 5. The process of recovery of the GABA ionophore from the desensitized state is distinct from the process of reactivation, which is dependent both on the voltage and agonist. 6. These observations suggest that the ligand-bound GABA receptor has two alternate states, i.e., permissive (activated) and desensitized. The rates of transition between these two states are voltage dependent.