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Intracellular calcium level is an important factor influencing ion channel modulations by PLC-coupled metabotropic receptors in hippocampal neurons
- Source :
- Brain Research. 1512:9-21
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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 M 1 -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.
- Subjects :
- Intracellular Fluid
Patch-Clamp Techniques
Time Factors
Muscarinic Antagonists
Muscarinic Agonists
Hippocampal neuron K+ channel
Hippocampus
Ion Channels
Methoxyhydroxyphenylglycol
Rats, Sprague-Dawley
Channel modulation
Phospholipase C
Muscarinic acetylcholine receptor
Potassium Channel Blockers
medicine
Animals
Calcium dependence
Drug Interactions
Channel blocker
Enzyme Inhibitors
Molecular Biology
Cells, Cultured
Ion channel
Anthracenes
Neurons
Dose-Response Relationship, Drug
Chemistry
Oxotremorine
General Neuroscience
Pirenzepine
Receptors, Muscarinic
Rats
Metabotropic receptor
Animals, Newborn
Apamin
Metabotropic glutamate receptor
Type C Phospholipases
Biophysics
Non-selective cation channel
Ligand-gated ion channel
Calcium
Neurology (clinical)
Neuroscience
Developmental Biology
medicine.drug
Subjects
Details
- ISSN :
- 00068993
- Volume :
- 1512
- Database :
- OpenAIRE
- Journal :
- Brain Research
- Accession number :
- edsair.doi.dedup.....d11f5e2f483432dca9e5f7550362e49c