@article{oai:kanazawa-u.repo.nii.ac.jp:00013990, author = {Sugawara, Yuto and Echigo, Ryousuke and Kashima, Kousuke and Minami, Hanae and Watanabe, Megumi and Nishikawa, Yuiko and Muranishi, Miho and Yoneda, Mitsugu and Ohno-Shosaku, Takako}, journal = {Brain Research}, month = {Jan}, note = {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 PLCβ activation depends on intracellular Ca2+ concentration ([Ca2+]i), suggesting the possibility that PLCβ-dependent cellular responses are basically Ca 2+ 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 [Ca 2+]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 [Ca 2+]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 PLCβ activation are basically Ca2+ dependent. © 2013 Elsevier B.V.}, pages = {9--21}, title = {Intracellular calcium level is an important factor influencing ion channel modulations by PLC-coupled metabotropic receptors in hippocampal neurons}, volume = {1512}, year = {2013} }