Physiological involvement of presynaptic L-type voltage-dependent calcium channels in GABA release of cerebellar molecular layer interneurons
Physiological involvement of presynaptic L-type voltage-dependent calcium channels in GABA release of cerebellar molecular layer interneurons
复制标题
突触前 L 型电压依赖性钙通道在小脑分子层中间神经元 GABA 释放中的生理作用
DOI：
10.1111/jnc.15100
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发表时间：
2020
影响因子：
4.7
通讯作者：
Collin T.
中科院分区：
文献类型：
--
作者：
Rey S.;Maton G.;Satake S.;Llano I.;Kang S.;Surmeier D. J.;Silverman R. B.;Collin T.
摘要尽管N和P/Q家族的高阈值电压依赖性钙通道(VDCC)对哺乳动物中枢神经递质的释放起关键作用，但目前尚不清楚主要作用于突触后部位的L型钙通道(LTCC)在多大程度上参与了递质释放的控制。在这里，我们研究了LTCCs在调节大鼠小脑分子层中间神经元(MLI)释放GABA方面的可能作用。我们发现，BayK8644(Bayk)显著增加MLIs和Purkinje细胞(PC)的mIPSC频率，表明LTCC在突触前表达。此外，我们观察到(1)在Bayk存在下对诱发的IPSCs有增强作用，(2)在LTCC特异性抑制剂化合物8(Cp8)的存在下抑制诱发的IPSCs，以及(3)Cp8显著降低mIPSC的频率。丹曲林可降低Bayk效应，提示兰尼定受体与LTCC具有协同作用。最后，Bayk增强了突触前AP诱发的钙瞬变，并增加了在TTX观察到的自发轴突钙瞬变的频率。综上所述，我们的数据表明，LTCC在调节MLI释放GABA方面起着首要作用。
AbstractWhile high threshold voltage‐dependent Ca2+channels (VDCCs) of the N and P/Q families are crucial for evoked neurotransmitter release in the mammalian CNS, it remains unclear to what extent L‐type Ca2+channels (LTCCs), which have been mainly considered as acting at postsynaptic sites, participate in the control of transmitter release. Here, we investigate the possible role of LTCCs in regulating GABA release by cerebellar molecular layer interneurons (MLIs) from rats. We found that BayK8644 (BayK) markedly increases mIPSC frequency in MLIs and Purkinje cells (PCs), suggesting that LTCCs are expressed presynaptically. Furthermore, we observed (1) a potentiation of evoked IPSCs in the presence of BayK, (2) an inhibition of evoked IPSCs in the presence of the LTCC‐specific inhibitor Compound 8 (Cp8), and (3) a strong reduction of mIPSC frequency by Cp8. BayK effects are reduced by dantrolene, suggesting that ryanodine receptors act in synergy with LTCCs. Finally, BayK enhances presynaptic AP‐evoked Ca2+transients and increases the frequency of spontaneous axonal Ca2+transients observed in TTX. Taken together, our data demonstrate that LTCCs are of primary importance in regulating GABA release by MLIs.