Pitler T A, Alger B E
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Neuron. 1994 Dec;13(6):1447-55. doi: 10.1016/0896-6273(94)90430-8.
Following postsynaptic activation of a pyramidal cell, the degree of GABAergic synaptic inhibition that the cell receives is reduced dramatically for many seconds. Previously, we found that induction of depolarization-induced suppression of inhibition (DSI) required post-synaptic increases in intracellular [Ca2+], but absence of a decrease in responsiveness to iontophoretically applied GABA left the mechanism of DSI expression uncertain. We investigated DSI with whole-cell voltage-clamp recordings in rat hippocampal slices. Bath-applied carbachol was ordinarily used to increase the spontaneous action potential-induced IPSCs (sIPSCs) and enhance detectability of DSI; synaptically released ACh has the same effects. TTX-sensitive sIPSCs are markedly reduced by DSI, whereas TTX-insensitive miniature IPSC amplitudes do not change, suggesting that DSI represents a retrograde influence on presynaptic GABA release. A lag (approximately 1 s) prior to maximal DSI and prevention of DSI by pertussis toxin pointed to a G protein-linked second messenger that may be presynaptic, since perturbation of postsynaptic G protein function did not alter DSI.
锥体细胞发生突触后激活后，该细胞所接受的GABA能突触抑制程度会在数秒内急剧降低。此前，我们发现，去极化诱导抑制（DSI）的诱导需要突触后细胞内[Ca2+]增加，但对离子导入施加的GABA反应性未降低，这使得DSI表达的机制仍不明确。我们在大鼠海马切片中用全细胞电压钳记录研究了DSI。通常使用浴加卡巴胆碱来增加自发动作电位诱导的抑制性突触后电流（sIPSCs）并增强DSI的可检测性；突触释放的乙酰胆碱也有相同作用。DSI可显著降低对河豚毒素（TTX）敏感的sIPSCs，而对TTX不敏感的微小抑制性突触后电流（mIPSCs）幅度不变，这表明DSI代表对突触前GABA释放的逆行影响。最大DSI出现前有一个延迟（约1秒），且百日咳毒素可阻止DSI，这表明存在一种可能位于突触前的G蛋白偶联第二信使，因为突触后G蛋白功能的扰动并未改变DSI。
