• nAChRα7

    repetitive activation by acetylcholine measured on the
    Patchliner


AChRa7 | nicotinic acetylcholine receptor alpha 7

Family:
Acetylcholine Receptors

Subgroups:
The family has been devided into nicotinic acetylcholine receptors (ionotropic channels) and muscarinic acetymcholine receptors (metabotropic G-protein coupled receptors). Both subgroups are sensitive to acetylcholine.

Topology:
Nicotinic acetylcholine receptors: As typical cys-loop receptors, acetylcholine receptor subunits contain four transmembrane spanning domains TM1-TM4. Five subunits form a pore, homomeric and heteromeric combinations are possible.17 vertebrate subunits have been identified: α genes: CHRNA1 - CHRNA10; β genes: CHRNB1 . CHRNB4, as well as CHRND (delta), CHRNE (epsilon), CHRNG (gamma)
Muscarinic acetylcholine receptors: 5 receptors have been described (M1 - M5), encoded by the 5 genes CHRM1 - CHRM5. These proteins contain seven transmembrane regions and do not form homo or heteromers. 

AChRα7: Background Information

Gene:
CHRNA7

Human Protein:
UniProt P36544

Tissue:
Brain, retina, spinal cord, peripheral neuronal tissues, including neurons of mammalian sympathetic ganglia, parasympathetic ganglia, sensory neurons such as the trigeminal ganglia and adrenal chromaffin cells

Function/ Application:
Mediates effects of acetylcholine and nicotine in specific regions of the brain, retina and spinal cord

Pathology:
Schizophrenia, Alzheimer's disease, Parkinson's, Tourette's Syndrome, depression

Accessory subunits:

Interaction:

Modulator:
Antagonists: DHβE, mecamylamine, α-bungarotoxin, α-conotoxin ImI, methyllycaconitine, α-conotoxin ArIB; Positive allosteric modulators: A-867744, LY2087101, NS1738, JNJ1930942, PNU-120596

Assays:
Patch Clamp: whole cell, room temperature, physiological temperature

Cell systems:
Stably-transfected GH4C1 cell line

Recommended Reviews:
Physiol Rev 89: 73–120, 2009; doi:10.1152/physrev.00015.2008, Albuquergue et al; Nicotinic acetylcholine receptors, in: Burger’s Medicinal Chemistry, Vol II Drug Discovery and Drug Development, Chapter 11, pp 357-405. Ed. Abraham, D., J. Wiley, New York., Colquhoun et al.

Testimonials

Dr. Thomas Seeger & Karin V. Niessen - Statement about the SURFE²R Technology

Icon N1   “The SURFE²R makes extremely challenging electrophysiological targets accessible to robust routine analyses. For example, we have developed an assay for investigating nicotinic acetylcholine receptor ion channels, using membranes from the Pacific electric ray, Torpedo California. In this way, we overcome many of the well-known difficulties associated with this ion channel, which allows us to efficiently obtain information regarding compound pharmacology. Obtained pharmacology values match those of patch clamp recordings exceptionally well. We find that the SURFE²R is an excellent platform for characterization of electrogenic processes in isolated membranes.”

Karin V. Niessen, Dr. Thomas Seeger
Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany

Application Notes

Acetylcholine Receptor Alpha 7 - "Human a7 nicotinic Acetylcholine Receptor on the Patchliner "

icon pl   Patchliner application note:   logo pdf   (0.2 MB)
Cells were kindly provided by Galantos.

Data and Applications

Acetylcholine Receptor Alpha 7 - Activation and Dose Response Curve

PL Nica7 DRicon pl   Patchliner data and applications:
Cells were kindly supplied by Galantos Pharma GmbH.

Complete nicotine dose response curves were obtained by applying increasing concentrations of nicotine to a HEK293 cell expressing human nicotinic α7 acetyl choline receptors. The stacked application protocol was used.

Acetylcholine Receptor Alpha 7 - Dose Response Curve

AChRCRCicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Galantos Pharma GmbH.

Increasing acetylcholine concentrations (30 µM, 100 µM and 300 µM) were added to the same cell using a stacked applications protocol. 

 

Acetylcholine Receptor Alpha 7 - Enhancement by NS1738

nACha7R PL NS1738 DRCicon pl   Patchliner data and applications:
Cells were kindly supplied by Galantos Pharma GmbH.

Concentration response curve for NS1738 co-applied with 300 μM ACh revealed an EC50 = 2.6 ± 1.1 μM (n = 4). This is in excellent agreement with the literature (Timmermann et al, 2007, JPET 323: 294–307).

Acetylcholine Receptor Alpha 7 - Enhancement of cabamoylcholine and epidatidine responses by PNU120596

ACha7 PNU Sheffelicon pl   Patchliner data and applications:
Cells were kindly supplied by Galantos Pharma GmbH.

Representative current records of carbamoylcholine- and epibatidine-induced nAChR activation in the absence and presence of PNU-120596. Horizontal bars indicate exposure time (233 ms) of compound(s) to the cell. Data from Scheffel et al, 2018.

Acetylcholine Receptor Alpha 7 - Enhancement of nicotine and acetylcholine responses by PNU120596

nACha7R PL PNU120596 scheffelicon pl   Patchliner data and applications:
Cells were kindly supplied by Galantos Pharma GmbH.

Representative current records of hα7-nAChR responses induced by nicotine and acetylcholine (ACh) (50, 100, 500 μM) in the absence (top) and presence of PNU-120596 (5, 10, 50 μM) (bottom). Horizontal bars indicate exposure time (233 ms) of compound(s). Data from Scheffel et al, 2018.

Acetylcholine Receptor Alpha 7 - Fast Solution Exchange

SyncronAChRicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:

Human nicotinic Acetylcholine receptors alpha 7 were activated by 100 µM Acetylcholine. Solution switch time was fast enough to detect Acetylcholine receptors alpha 7 responses.

 

Acetylcholine Receptor Alpha 7 - PNU Modulation

PNU Syncroicon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Galantos Pharma GmbH.

After the desensitization of the nAChR a7 receptor by 100 µM acetylcholine, 10 µM PNU-120596 was applied together with 100 µM of Ach, reactivating the ion channels.

 

Acetylcholine Receptor Alpha 7 - Stable nicotine responses

icon pl   Patchliner data and applications: nAChRa7 repetitive PL
Cells were kindly supplied by Galantos Pharma GmbH.

Stable whole-cell current amplitudes were obtained by repeated 100 mM nicotine stimulation of HEK293 cells expressing human nACha7 receptors. The stacked application protocol was used. 

Publications

2018 - In vitro pharmacological characterization of the bispyridinium non-oxime compound MB327 and its 2- and 3-regioisomers

Icon 96SE  SURFE²R 96SE publication in Toxicology Letters (2018)

Authors: 
Niessen K.V., Seeger T. Rappenglück S., Wein T., Höfner G., Wanner K.T., Thiermanna H., Worek F.

2018 - Electrophysiological investigation of the effect of structurally different bispyridinium non-oxime compounds on human α7-nicotinic acetylcholine receptor activity - An in vitro structure-activity analysis

icon pl   Patchliner publication in Toxicology Letters (2018)

Authors:
Scheffel C., Niessen K.V., Rappenglück S., Wanner K.T., Thiermann H., Worek F., Seeger T.

2018 - Counteracting desensitization of human α7-nicotinic acetylcholine receptors with bispyridinium compounds as an approach against organophosphorus poisoning

icon pl   Patchliner publication in Toxicology Letters (2018)

Authors:
Scheffel C., Niessen K.V., Rappenglück S., Wanner K.T., Thiermann H., Worek F., Seeger T.

2016 - Functional analysis of Torpedo californica nicotinic acetylcholine receptors in multiple activation states by SSM-based electrophysiology

Icon 96SE   SURFE²R N96 (predesessor model of SURFE²R 96SE) publication in Toxicological Letters (2016)

Authors: 
Niessen K.V., Muschik S., Langguth F., Rappenglück S., Seeger T., Thiermann H., Worek F.

2015 - Novel screening techniques for ion channel targeting drugs

icon pl  Patchliner,   icon sp96   SyncroPatch 384PE and   Icon CE   CardioExcyte 96 publication in Channels (2015)

Authors: 
Obergrussberger A., Stölzle-Feix S., Becker N., Brüggemann A., Fertig N., Möller C.

2014 - Automated Patch Clamp Analysis of nAChα7 and NaV1.7 Channels

icon pap  Port-a-Patch and   icon pl   Patchliner publication in Current Protocols in Pharmacology (2014)

Authors: 
Obergrussberger A., Haarmann C., Rinke I., Becker N., Guinot D., Brueggemann A., Stoelzle-Feix S., George M., Fertig N.

2013 - Automated Planar Patch Clamp

icon pl   Patchliner book chapter in Ion Channels (2013)

Authors: 
Milligan, C. J., Möller, C.

2011 - State-of-the-art automated patch clamp devices: heat activation, action potentials, and high throughput in ion channel screening

icon pap   Port-a-Patch,   icon pl  Patchliner and   icon sp96   SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) publication in Frontiers in Pharmacology (2011)

Authors: 
Stoelzle S., Obergrussberger A., Brüggemann A., Haarmann C., George M., Kettenhofen R., Fertig N.

 

 

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