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2018 - Label-free analysis of Na+/Ca2+- exchanger (NCX) isolated from iPSC-derived cardiomyocytes

Icon N1   SURFE²R N1 and   Icon 96SE   SURFE2R 96SE poster, Europhysiology Meeting 2018  logo pdf   (1.5 MB)

 

Abstract:

The Sodium-Calcium Exchangers (NCX) play an important role in the cellular calcium homeostasis under physiological and pathological conditions. NCX has been of interest as a pharmacological target for many years, in particular because clinical trials involving inhibitors of the sodium-proton exchanger, NHE, have delivered mixed results. Inhibition of the reversed mode of NCX is thought to be beneficial in ischemia/reperfusion injury by reducing cardiac, neuronal and renal infarct areas. Moreover, inhibition of NCX has been proposed to exhibit an anti-arrhythmic effect and therefore, may provide a novel target for the treatment of a variety of arrhythmic pathologies. So far, a number of studies have shown promising results but investigations are limited by the currently available NCX inhibitors such as KB-R7943, SEA-0400 and SN-6 which are only partially specific.

To drive the progress in pharmacological NCX research, new methods to measure NCX function are needed. At the current time, functional investigation of NCX range from patch-clamp, calcium flux assays, Langendorffperfused hearts to studies in whole animals. We have developed an electrophysiological method to investigate NCX function which is based on the solid supported membrane (SSM) technology. HEK cells overexpressing NCX or human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used on a single-well or 96-well SSM electrophysiology device and NCX was recorded from these cells. NCX was activated using Ca2+ in the buffer and inhibited by Cd2+ and other compounds. 

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