title: Intracellular calcium level is an important factor influencing ion channel modulations by PLC-coupled metabotropic receptors in hippocampal neurons.
abstract: 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 Ca(2+) concentration ([Ca(2+)]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 [Ca(2+)]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 [Ca(2+)]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 [Ca(2+)]i, supporting the hypothesis that cellular responses induced by receptor-driven PLCβ activation are basically Ca(2+) dependent.
authors.affiliation: Faculty of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-0942, Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Echigo
authors.forename: Kousuke
authors.initials: K
authors.lastname: Kashima
authors.forename: Hanae
authors.initials: H
authors.lastname: Minami
authors.forename: Megumi
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Miho
authors.initials: M
authors.lastname: Muranishi
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Yoneda
authors.forename: Takako
authors.initials: T
authors.lastname: Ohno-Shosaku
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000873:Anthracenes / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010890:Pirenzepine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013997:Time Factors; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D004791:Enzyme Inhibitors; D007473:Ion Channels; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D026902:Potassium Channel Blockers; D011976:Receptors, Muscarinic; D001030:Apamin; D010890:Pirenzepine; D008734:Methoxyhydroxyphenylglycol; D010095:Oxotremorine; C042743:oxotremorine M; D010738:Type C Phospholipases; D002118:Calcium; C010117:3,4-dihydroxyphenylglycol