NDLI: Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics

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Molecular mechanisms of biomaterial-driven osteogenic differentiation in human mesenchymal stromal cells

Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics

Molecular network analysis of phosphotyrosine and lipid metabolism in hepatic PTP1b deletion mice

Astrocyte–neuron co-culture on microchips based on the model of SOD mutation to mimic ALS

Live imaging reveals active infiltration of mitotic zone by its stem cell niche

Influence of pressurized cyclic stretch and endothelial cell presence on multipotent stem cell osteogenic commitment

Large particle multiphoton flow cytometry to purify intact embryoid bodies exhibiting enhanced potential for cardiomyocyte differentiation

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Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics

Content Provider	Royal Society of Chemistry (RSC)
Author	Wade, Susan M. Takayama, Shuichi Neubig, Richard R. Jovic, Andreja Linderman, Jennifer J.
Copyright Year	2013
Abstract	Through microfluidic interrogation we analyzed real-time calcium responses of HEK293 cells stimulated with short pulses of the M3 muscarinic receptor ligand carbachol in two different concentration regimes. Lower ligand concentrations elicit oscillatory calcium signals while higher concentrations trigger a rapid rise that eventually settles down at a steady-state slightly above pre-stimulus levels, referred to as an acute signal. Cells were periodically pulsed with carbachol at these two concentration regimes using a custom-made microfluidic platform, and the resulting calcium signals were measured with a single fluorescent readout. Pulsed stimulations at these two concentration regimes resulted in multiple types of response patterns that each delivered complementary information about the M3 muscarinic receptor signaling pathway. These multiple types of calcium response patterns enabled development of a comprehensive mathematical model of multi-regime calcium signaling. The resulting model suggests that dephosphorylation of deactivated receptors is rate limiting for recovery of calcium signals in the acute regime (high ligand concentration), while calcium replenishment and IP3 production determine signal recovery in the oscillatory regime (low ligand concentration). This study not only provides mechanistic insight into multi-regime signaling of the M3 muscarinic receptor pathway, but also provides a general strategy for analyzing multi-regime pathways using only one fluorescent readout.
Starting Page	932
Ending Page	939
Page Count	8
File Format	HTM / HTML PDF
ISSN	17579694
Volume Number	5
Issue Number	7
Journal	Integrative Biology
DOI	10.1039/c3ib40032h
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Calcium Muscarinic acetylcholine receptor M3 Ligand Carbachol Mathematical model Calcium signaling Phospholipase C
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Biophysics

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Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics

The m3 muscarinic acetylcholine receptor differentially regulates calcium influx and release through modulation of monovalent cation channels.

Dissecting the conserved NPxxY motif of the M3 muscarinic acetylcholine receptor: critical role of Asp-7.49 for receptor signaling and multiprotein complex formation.

Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes.

Accelerated molecular dynamics simulations of ligand binding to a muscarinic G-protein-coupled receptor

Chronic exposure to the anti-M3 muscarinic acetylcholine receptor autoantibody in pemphigus vulgaris contributes to disease pathophysiology.

Rapid and Persistent Desensitization of m3 Muscarinic Acetylcholine Receptor-stimulated Phospholipase D CONCOMITANT SENSITIZATION OF PHOSPHOLIPASE C

Homology modelling of the structure of human m3 muscarinic acetylcholine receptor.

Evidence for ADP-Ribosylation-Factor-Mediated Activation of Phospholipase D by m3 Muscarinic Acetylcholine Receptor

Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics

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Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics

The m3 muscarinic acetylcholine receptor differentially regulates calcium influx and release through modulation of monovalent cation channels.

Dissecting the conserved NPxxY motif of the M3 muscarinic acetylcholine receptor: critical role of Asp-7.49 for receptor signaling and multiprotein complex formation.

Muscarinic acetylcholine receptor subtypes as agonist-dependent oncogenes.

Accelerated molecular dynamics simulations of ligand binding to a muscarinic G-protein-coupled receptor

Chronic exposure to the anti-M3 muscarinic acetylcholine receptor autoantibody in pemphigus vulgaris contributes to disease pathophysiology.

Rapid and Persistent Desensitization of m3 Muscarinic Acetylcholine Receptor-stimulated Phospholipase D CONCOMITANT SENSITIZATION OF PHOSPHOLIPASE C

Homology modelling of the structure of human m3 muscarinic acetylcholine receptor.

Evidence for ADP-Ribosylation-Factor-Mediated Activation of Phospholipase D by m3 Muscarinic Acetylcholine Receptor

Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics