Retrograde signalling in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells
Retrograde signalling in depolarization-induced suppression of inhibition in rat hippocampal CA1 cells
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DOI：
10.1113/jphysiol.1996.sp021677
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发表时间：
1996-10-01
影响因子：
5.5
通讯作者：
Lenz, RA
中科院分区：
文献类型：
--
作者：
Alger, BE;Pitler, TA;Lenz, RA
1.采用全细胞电压钳技术，观察了大鼠海马脑片CA 1区锥体细胞的去极化抑制现象。DSI通过引发电压依赖性钙（Ca 2+）电流诱导，电压步长为1 s，从保持电位+60 mV至+90 mV。DXI在电压阶跃后约1分钟的时间内明显表现为突触GABA（A）反应的减少。TTX敏感的自发性IPSCs（sIPSCs）对DSI敏感，而TTX抗性的微小抑制性突触后电流（mIPSCs）对DSI不敏感。微型IPSC通常是罕见的，独立于外部的Ca 2+在CA 1区。为了增加mIPSCs的频率并诱导Ca 2+敏感的mIPSCs群体，我们将浴中K+浓度增加到15 mM。然而，增加的mIPSCs对DSI也不敏感。全细胞移液器填充溶液含有5 mM 2-（三乙基氨基-N-（2，6-二甲基苯基）乙酰胺（QX-314）以阻断电压依赖性Na+电流和铯以阻断K+电流。然而，50 μ M 4-氨基吡啶（4-AP）或250 nM藜芦啶的浴涂都明显降低了DSI，显然是通过作用于突触前位点。在DSI期间，单合成诱发的IPSC（在10 μ M 6-氰基-7-硝基喹喔啉-2，3-二酮（ChQX）和50 μ M 2-氨基-5-膦酰基戊酸（APV）存在下诱发）的振幅显著降低。弱刺激产生小的IPSC和偶尔的“故障”的传输在控制期间。在DSI期间，失败的百分比显著增加。中等强度的刺激产生较大的IPSC，通常由可区分的多量子成分组成。在DSI.5期间，多量子IPSC组件也发生了全失效或无失效。双脉冲IPSC抑郁的程度在DSI期间没有改变，而巴氯芬如预期的那样降低了。6.我们的结论是，数据代表新的证据表明，DSI介导的逆行信号传导过程可能涉及突触前轴突传导阻滞。
1. We have investigated the phenomenon of 'depolarization-induced suppression of inhibition' (DSI) using whole-cell voltage-clamp techniques in CA1 pyramidal cells of rat hippocampal slices. DSI was induced by eliciting voltage-dependent calcium (Ca2+) currents with 1 s voltage steps of +60 to +90 mV from the holding potential. DXI was apparent as a reduction in synaptic GABA(A) responses for a period of about 1 min following the voltage step.2. TTX-sensitire spontaneous IPSCs (sIPSCs) were susceptible to DSI, while TTX-resistant miniature inhibitory postsynaptic currents (mIPSCs) were not. Miniature IPSCs are ordinarily infrequent and independent of external Ca2+ in the CA1 region. To increase the frequency of mIPSCs and to induce a population of Ca2+ sensitive mIPSCs, we increased the bath K+ concentration to 15 mM. The increased mIPSCs were also insenstive to DSI, however.3. The whole-cell pippette-filling solution contained 5 mM 2(triethylamino-N-(2,6-dimethylphenyl)acetamide (QX-314) to block voltage-dependent Na+ currents and caesium to block K+ currents. Nevertheless, bath application of 50 mu 4-aminopyridine (4-AP) or 250 nM veratridine both clearly reduced DSI, evidently by acting at presynaptic sites.4. The amplitudes of monosynatically evoked IPSCs (elicited in the presence of 10 mu M 6-cyano-7-nitroquinoxaline-2,3-dione (ChQX) and 50 mu M 2-amino-5-phosphonovaleric acid (APV)) were dramatically reduced during the DSI period. Weak stimulation produced small IPSCs and occasional 'failures' of transmission during the control period. The percentage of failures increased markedly during the DSI period. Moderate-intensity stimulation produced larger IPSCs that were often composed of distinguishable multiquantal components. All-or-none failures of multiquantal IPSC components also occurred during DSI.5. The degree of paired-pulse IPSC depression did not change during DSI, whereas it was decreased, as expected, by baclofen. 6. We conclude that the data represent novel evidence that DSI is mediated by a retrograde signalling process possibly involving presynaptic axonal conduction block.