DESENSITIZED STATES PROLONG GABA(A) CHANNEL RESPONSES TO BRIEF AGONIST PULSES
DESENSITIZED STATES PROLONG GABA(A) CHANNEL RESPONSES TO BRIEF AGONIST PULSES
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DOI：
10.1016/0896-6273(95)90075-6
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发表时间：
1995-07-01
期刊：
影响因子：
16.2
通讯作者：
WESTBROOK, GL
中科院分区：
文献类型：
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作者：
JONES, MV;WESTBROOK, GL
我们通过比较非平衡GABA（A）通道门控和抑制性突触后电流（IPSC）来研究抑制性突触脱敏的作用。由1-10 mM GABA的短暂脉冲激活的电流，从培养的海马神经元向外的补丁模仿GABA介导的IPSC。虽然短暂脉冲后单个GABA（A）通道的平均开放时间小于10 ms，但通道进入长时间（tau = 38-69 ms）关闭状态，随后重新开放。通过这些状态的运动导致成对脉冲脱敏。去除激动剂后失活所需的时间也与脱敏的程度成比例增加。这些结果表明，对脱敏状态的访问缓冲了束缚构象中的通道，并成为IPSC持久成分表达的基础。GABA（A）受体脱敏后的重新开放可能会通过延长对短暂突触GABA瞬变的反应来增强抑制性突触传递。
We studied the role of desensitization at inhibitory synapses by comparing nonequilibrium GABA(A) channel gating with inhibitory postsynaptic currents (IPSCs). Currents activated by brief pulses of 1-10 mM GABA to outside-out patches from cultured hippocampal neurons mimicked GABA-mediated IPSCs. Although the average open time of single GABA(A) channels following brief pulses was less than 10 ms, channels entered long (tau = 38-69 ms) closed states and subsequently reopened. Movement through these states resulted in paired-pulse desensitization. The time required for deactivation after removal of agonist also increased in proportion to the extent of desensitization. These results suggest that visits to desensitized states buffer the channel in bound conformations and underlie the expression of long-lasting components of the IPSC. Reopening after GABA(A) receptor desensitization may thus enhance inhibitory synaptic transmission by prolonging the response to a brief synaptic GABA transient.