Department of Physiology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Korean J Physiol Pharmacol. 2012 Apr;16(2):139-44. doi: 10.4196/kjpp.2012.16.2.139. Epub 2012 Apr 24.
It has been reported that activation of metabotropic glutamate receptor 1 (mGluR1) can mediate endocannabinoid-induced short-term depression of synaptic transmission in cerebellar parallel fiber (PF)-Purkinje cell (PC) synapse. mGluR1 has signaling pathways involved in intracellular calcium increase which may contribute to endocannabinoid release. Two major mGluR1-evoked calcium signaling pathways are known: (1) slow-kinetic inward current carried by transient receptor potential canonical (TRPC) channel which is permeable to Ca(2+); (2) IP(3)-induced calcium release from intracellular calcium store. However, it is unclear how much each calcium source contributes to endocannabinoid signaling. Here, we investigated whether calcium influx through mGluR1-evoked TRPC channel contributes to endocannabinoid signaling in cerebellar Purkinje cells. At first, we applied SKF96365 to inhibit TRPC, which blocked endocannabinoid-induced short-term depression completely. However, an alternative TRP channel inhibitor, BTP2 did not affect endocannabinoid-induced short-term depression although it blocked mGluR1-evoked TRPC currents. Endocannabinoid signaling occurred normally even though the TRPC current was mostly blocked by BTP2. Our data imply that TRPC current does not play an important role in endocannabinoid signaling. We also suggest precaution in applying SKF96365 to inhibit TRP channels and propose BTP2 as an alternative TRPC inhibitor.
已有报道称，代谢型谷氨酸受体 1（mGluR1）的激活可以介导小脑平行纤维（PF）-浦肯野细胞（PC）突触中内源性大麻素诱导的突触传递短期抑制。mGluR1 具有涉及细胞内钙离子增加的信号通路，这可能有助于内源性大麻素的释放。已知 mGluR1 诱导的两个主要钙离子信号通路为：（1）由瞬时受体电位经典型（TRPC）通道携带的慢动力学内向电流，该通道对 Ca（2+）具有通透性；（2）来自细胞内钙库的 IP3 诱导的钙释放。然而，目前尚不清楚每种钙源对内源性大麻素信号的贡献有多少。在这里，我们研究了通过 mGluR1 诱导的 TRPC 通道的钙内流是否有助于小脑浦肯野细胞中的内源性大麻素信号。首先，我们应用 SKF96365 抑制 TRPC，这完全阻断了内源性大麻素诱导的短期抑制。然而，尽管阻断了 mGluR1 诱导的 TRPC 电流，替代的 TRP 通道抑制剂 BTP2 并未影响内源性大麻素诱导的短期抑制。尽管 BTP2 大部分阻断了 TRPC 电流，但内源性大麻素信号仍正常发生。我们的数据表明，TRPC 电流在内源性大麻素信号中不起重要作用。我们还建议在应用 SKF96365 抑制 TRP 通道时要谨慎，并提出 BTP2 作为替代的 TRPC 抑制剂。
