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

• Published in: Brain research 2013-05, Vol.1512, p.9-21
• Main Authors: Sugawara, Yuto, Echigo, Ryousuke, Kashima, Kousuke, Minami, Hanae, Watanabe, Megumi, Nishikawa, Yuiko, Muranishi, Miho, Yoneda, Mitsugu, Ohno-Shosaku, Takako
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; antagonists; Anthracenes - pharmacology; Apamin - pharmacology; Biological and medical sciences; brain; calcium; Calcium - metabolism; Calcium dependence; Cells, Cultured; Central nervous system; Channel modulation; Dose-Response Relationship, Drug; Drug Interactions; Electrophysiology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; glutamic acid; Hippocampal neuron; Hippocampus - cytology; Intracellular Fluid - drug effects; Intracellular Fluid - metabolism; ion channels; Ion Channels - metabolism; K+ channel; Methoxyhydroxyphenylglycol - analogs & derivatives; Methoxyhydroxyphenylglycol - pharmacology; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - pharmacology; Neurology; neurons; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Non-selective cation channel; Oxotremorine - analogs & derivatives; Oxotremorine - pharmacology; Patch-Clamp Techniques; Phospholipase C; Pirenzepine - pharmacology; Potassium Channel Blockers - pharmacology; Rats; Rats, Sprague-Dawley; receptors; Receptors, Muscarinic - metabolism; signal transduction; Time Factors; Type C Phospholipases - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2013.03.040

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 Ca2+ concentration ([Ca2+ ]i ), suggesting the possibility that PLCβ-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 PLCβ activation are basically Ca2+ dependent.