Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity.
Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity.
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DOI：
10.1155/2016/1239629
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发表时间：
2016
影响因子：
3.1
通讯作者：
Isokawa M
中科院分区：
文献类型：
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作者：
Isokawa M
GABA能抑制在神经元兴奋性的调节中起着至关重要的作用；因此，它受到许多因素的调节。最近的证据表明细胞内钙 ([Ca2+]i) 和钙依赖性信号分子的升高是调节的基础。咖啡因会诱导细胞内储存的钙释放。我们测试了咖啡因是否通过增加 [Ca2+]i 来调节 GABA 能传递。向海马 CA1 锥体细胞短暂局部喷洒咖啡因，可暂时抑制 GABA 能抑制性突触后电流 (IPSC) 73.2 ± 6.98%。 IPSC 的抑制时间过程和随后的恢复类似于 DSI（去极化诱导的抑制抑制），由需要 [Ca2+]i 升高的内源性大麻素介导。然而，与 DSI 不同，咖啡因诱导的 IPSCs (CSI) 抑制在[Ca2+]i 不增加的情况下持续存在。细胞内应用 BAPTA 和兰尼定（可阻止咖啡因诱导的细胞内钙释放）未能阻止 CSI 的产生。令人惊讶的是，钌红是一种多种钙渗透/释放通道（包括储存通道）的抑制剂，通过独立于钙放大 CSI 的大小来诱导化塑性。这种化塑性伴随着大的内向电流的产生。尽管这种内向电流的离子基础尚未确定，但目前的结果表明，咖啡因对 GABA 能抑制具有强大的 Ca2+ 独立抑制作用，并通过打开质膜通道引起化塑性。
GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i) and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs) by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition), mediated by endogenous cannabinoids that require a [Ca2+]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI) persisted in the absence of a [Ca2+]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores) failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.