xe-991--anthracenone and 3-4-dihydroxyphenylglycol

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.

Topics: Animals; Animals, Newborn; Anthracenes; Apamin; Calcium; Cells, Cultured; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors; Hippocampus; Intracellular Fluid; Ion Channels; Methoxyhydroxyphenylglycol; Muscarinic Agonists; Muscarinic Antagonists; Neurons; Oxotremorine; Patch-Clamp Techniques; Pirenzepine; Potassium Channel Blockers; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Time Factors; Type C Phospholipases