Intracellular calcium level is an important factor influencing ion channel modulations by PLC-coupled metabotropic receptors in hippocampal neurons

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• 作者：Yuto Sugawara ; Ryousuke Echigo ; Kousuke Kashima ; Hanae Minami ; Megumi Watanabe ; Yuiko Nishikawa ; Miho Muranishi ; Mitsugu Yoneda ; Takako Ohno-Shosaku ; ^{shosaku@med.kanazawa-u.ac.jp} ; ^{shosaku@mhs.mp.kanazawa-u.ac.jp}
• 关键词：[Ca2+]i ; intracellular Ca2+ concentration ; FFA ; flufenamic acid ; I-mGluR ; Group I metabotropic glutamate receptor ; NSC ; non-selective cation ; Oxo-M ; oxotremorine M ; PLC ; phospholipase C ; TTX ; tetrodotoxin
• 刊名：Brain Research
• 出版年：2013
• 出版时间：28 May, 2013
• 年：2013
• 卷：1512
• 期：Complete
• 页码：9-21
• 全文大小：885 K

文摘

Signaling pathways involving phospholipase C (PLC) are involved in various neural functions. Understanding how these pathways are regulated will lead to a better understanding of their roles in neural functions. Previous studies demonstrated that receptor-driven PLC¦Â activation depends on intracellular Ca²⁺ concentration ([Ca²⁺]_i), suggesting the possibility that PLC¦Â-dependent cellular responses are basically Ca²⁺ dependent. To test this possibility, we examined whether modulations of ion channels driven by PLC-coupled metabotropic receptors are sensitive to [Ca²⁺]_i using cultured hippocampal neurons. Muscarinic activation triggered an inward current at ?100 mV (the equilibrium potential for K⁺) in a subpopulation of neurons. This current response was suppressed by pirenzepine (an M₁-preferring antagonist), PLC inhibitor, non-selective cation channel blocker, and lowering [Ca²⁺]_i. Using the neurons showing no response at ?100 mV, effects of muscarinic activation on K⁺ channels were examined at ?40 mV. Muscarinic activation induced a transient decrease of the holding outward current. This current response was mimicked and occluded by XE991, an M-current K⁺ channel blocker, suppressed by pirenzepine, PLC inhibitor and lowering [Ca²⁺]_i, and enhanced by elevating [Ca²⁺]_i. Similar results were obtained when group I metabotropic glutamate receptors were activated instead of muscarinic receptors. These results clearly show that ion channel modulations driven by PLC-coupled metabotropic receptors are dependent on [Ca²⁺]_i, supporting the hypothesis that cellular responses induced by receptor-driven PLC¦Â activation are basically Ca²⁺ dependent.