Differential Coupling of Alpha7 and Non-alpha7 Nicotinic Acetylcholine Receptors to Calcium-induced Calcium Release and Voltage-operated Calcium Channels in Pc12 Cells.
From: Department of Biology & Biochemistry, University of Bath, Bath, UK.
Journal of neurochemistry
- Publish Date: Feb 2007
- ISSN: 0022-3042
- Volume: 100
- Issue: 4
- Pages: 1089-96
- Medium: Print
- Language: English
- Citation (JAMA): Dickinson Jane A, Hanrott Katharine E, Mok M H Selina, et al. Differential Coupling of Alpha7 and Non-alpha7 Nicotinic Acetylcholine Receptors to Calcium-induced Calcium Release and Voltage-operated Calcium Channels in Pc12 Cells.. J. Neurochem. Feb 2007;100:1089-96
Abstract
Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels that can modulate various neuronal processes by altering intracellular Ca(2+) levels. Following nAChR stimulation Ca(2+) can enter cells either directly, through the intrinsic ion channel, or indirectly following voltage-operated Ca(2+) channel (VOCC) activation; Ca(2+) levels can subsequently be amplified via Ca(2+)-induced Ca(2+) release from intracellular stores. We have used subtype-selective nAChR agonists to investigate the Ca(2+) sources contributing to alpha7 and non-alpha7 nAChR-mediated increases in intracellular Ca(2+) in PC12 cells. Application of the alpha7 nAChR positive allosteric modulator PNU 120596 (10 mum), in conjunction with the alpha7 nAChR agonist, compound A [(R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiophene-2-carboxamide), 10 nm], produces a rapid increase in fluo-3 fluorescence that is prevented by the selective alpha7 nAChR antagonist alpha-bungarotoxin. The non-alpha7 nAChR agonist 5-Iodo-A-85380 produces alpha-bungarotoxin-insensitive increases in intracellular Ca(2+) (EC(50) = 11.2 mum). Using these selective agonists or KCl in conjunction with general and selective VOCC inhibitors, we demonstrate that the primary route of Ca(2+) entry following either non-alpha7 nAChR activation or KCl stimulation is via L-type VOCCs. In contrast, the alpha7 nAChR-mediated response is unaffected by VOCC blockers but is inhibited by modulators of intracellular Ca(2+) stores. These results indicate that alpha7 and non-alpha7 nAChRs are differentially coupled to Ca(2+)-induced Ca(2+) release and VOCCs, respectively.
Mesh Headings (Keywords): Animals, Calcium, Calcium Channel Blockers, Calcium Channels, Calcium Signaling, Cholinergic Agonists, Cholinergic Antagonists, Dose-Response Relationship, Drug, Drug Interactions, Extracellular Fluid, Models, Biological, PC12 Cells, Potassium Chloride, Radioligand Assay, Rats, Receptors, Nicotinic, Ryanodine
Check for Full Text / PubMed Unique Identifier (PMID): 17181555
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