25.02.2021 - A deep-dive into NCX
NCX Family / Sodium-Calcium-Exchangers
Family:
Calcium-Cation Antiporter family (CaCA)
Subgroups:
The CaCA superfamily is composed of five families: K+-independent Na+/Ca2+ exchangers (NCXs), cation/Ca2+ exchangers (CCXs), YbrG transporters and cation exchangers (CAXs). Phylogenetic and alignment studies indicate that one of the mammalian NCKXs, NCKX6, and its related proteins form a unique group, designated cation/Ca2+ exchangers (CCXs)
Topology:
Proteins of the CaCA family are found ubiquitously, having been identified in animals, plants, yeast, archaea and divergent bacteria. They exhibit widely divergent sequences, and several have been shown to have arisen by a tandem intragenic duplication event. The most conserved portions of this repeat element, α1 and α2, are found in putative transmembrane regions 2-3 and transmembrane regions 7-8. Members of this family contain nine transmembrane regions in mammals.
Function:
All of the characterized animal proteins catalyze Ca2+:Na+ exchange although some also transport K+. The NCX plasma membrane proteins exchange 3 Na+ for 1 Ca2+. Mammalian Na+/Ca2+ exchangers exist as three isoforms NCX1-3 which are about 70% identical to each other.
Read this detailed publication, with functional data on purified NCX_Mj using solid supported membrane (SSM)-based electrophysiology
Learn more from this Poster about Drug Effects on human Na+/Ca2+ Exchanger and Implications for Drug Development, find out how to access more scientific content presented at Biophysical Society Meeting 2021 here.
Find out more about NCX1
Data and Applications
NCX1 - High Throughput Screening on the SURFE2R 96SE
SURFE2R 96SE data and applications:
Cells were kindly provided by Charles River.
NCX1 over-expressed in HEK cells was recorded on the SURFE2R 96SE. A membrane preparation of HEK cells expressing NCX1 was used on the SURFE2R 96SE. An activating buffer containing 100 μM Ca2+ was used to activate NCX1 (black and dark blue traces) after a negative control (0 Ca2+; light blue trace). NCX1 was activated three times after which a pharmacological experiment can be started to test for inhibitors. Wells are color-coded so that the user can get an overview of the succes of the experiment at a glance. Green wells depict resistance >500 MΩ, blue depicts wells have a resistance between 100 and 500 MΩ.
NCX1 - Effect of block of cardiac NCX on beat rate
CardioExcyte data and applications:
Cells were kindly provided by Cellular Dynamics.
Block of NCX1 expressed in iCell® Cardiomyocytes2 by SEA 0400 caused a dose dependent increase in beat rate.
NCX1 - Block by SEA0400
SURFE2R N1 data and applications:
Cardiac NCX1 expressed in iCell® Cardiomyocytes2 or HEK cells was blocked by increasing concentrations of SEA0400, a specific blocker of NCX.
NCX1 - Block by KB-R7943
SURFE2R N1 data and applications:
Cardiac NCX1 expressed in iCell® Cardiomyocytes2, Cor.4U® Cardiomyocytes or HEK cells was blocked by increasing concentrations of KB-R7943.
Posters
2021 - Drug Effects on human Na+/Ca2+ Exchanger and Implications for Drug Development.
FLEXcyte 96 and 
SURFE²R N1 and 
SURFE²R 96SE poster, Biophysical Society Meeting 2021 
(1.3 MB)
2020 - A novel approach to detect electrogenic transporter activity in intact cells applied to investigate iPSC derived cardiomyocytes and neurons
SURFE²R N1 and SURFE²R 96SE poster, 64th Annual Meeting of the Biophysical Society (1.6 MB)
2018 - Transported by light: optogenetic control of NCX1
SURFE²R N1 poster, Biophysics Annual Meeting 2018 (2.2 MB)
2018 - Label-free analysis of Na+/Ca2+- exchanger (NCX) isolated from iPSC-derived cardiomyocytes
SURFE²R N1 and SURFE2R 96SE poster, Europhysiology Meeting 2018 (1.5 MB)
2017 - High throughput real-time measurement of electrogenic membrane transport driven by the SLC transporters PepT1 and OcT2
SURFE²R SE96 poster, Biophysics congress 2017 (1.8 MB)
Publications
2016 - Electrophysiological characterization of the archaeal transporter NCX_Mj using solid supported membrane technology
SURFE²R N1 and 
Vesicle Prep Pro publication in Journal of General Physiology (2016)
Authors:
Barthmes M., Liao J., Jiang Y., Brüggemann A., Wahl-Schott C.
2006 - Transporter assays using solid supported membranes: a novel screening platform for drug discovery
SURFE²R ONE (a predecessor model of SURFE²R N1) publication in ASSAY and Drug Development Technologies (2006)
Authors:
Kelety B., Diekert K., Tobien J., Watzke N., Dörner W., Obrdlik P., Fendler K.
2006 - Establishment of Cell-Free Electrophysiology for Ion Transporters: Application for Pharmacological Profiling
SURFE²R ONE (a predecessor model of SURFE²R N1) publication in Journal of Biomolecular Screening (2006)
Authors:
Geibel S., Flores-Herr N., Licher T., Vollert H.
Find out more about NCX_Mj
Data and Applications
NCX_Mj - EC50 for Calcium and Magnesium
SURFE2R N1 data and applications:
Measurement of the transport activity of NCX_Mj. The first solution exchange provides a Na+-free solution to establish an outward directed Na+ gradient; the second solution exchange provides the divalent cation to activate the ion exchanger. By applying different concentrations of one divalent cation on the same sensor, we determined EC50 for Ca2+, Mg2+ and Sr2+.
Posters
2017 - An emerging technique for the characterization of transport proteins: SSM-based electrophysiology
SURFE²R N1 and SURFE²R SE96 poster, 19th IUPAB / 11th EBSA congress 2017 (3.3 MB)
2015 - Functional Characterization of Prokaryotic NCX by Solid Supported Membrane Technology
SURFE²R N1 poster, Gordon Research Conference 2015 (0.9 MB)
Publications
2016 - Electrophysiological characterization of the archaeal transporter NCX_Mj using solid supported membrane technology
SURFE²R N1 and Vesicle Prep Pro publication in Journal of General Physiology (2016)
Authors:
Barthmes M., Liao J., Jiang Y., Brüggemann A., Wahl-Schott C.