[en] The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood. Here, we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. In addition to this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties. Both the Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single-digit range, can be detected through transcriptome analysis of reticulocytes. Proteomics analysis of reticulocytes and mature RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch clamp method. While for the Gárdos channel, the activity in terms of ion currents is higher in reticulocytes compared to mature RBCs, for Piezo1, the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs. We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis.
Disciplines :
Physical, chemical, mathematical & earth Sciences: Multidisciplinary, general & others
Author, co-author :
Petkova-Kirova, Polina ; Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria ; Department of Biochemistry, Saarland University, 66123 Saarbrücken, Germany
Murciano, Nicoletta ; Nanion Technologies, 80339 Munich, Germany ; Theoretical Medicine and Biosciences, Campus University Hospital, Saarland University, 66421 Homburg, Germany
Iacono, Giulia ; Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands ; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1007 MB Amsterdam, The Netherlands
Jansen, Julia; Theoretical Medicine and Biosciences, Campus University Hospital, Saarland University, 66421 Homburg, Germany ; Department of Experimental Physics, Saarland University, 66123 Saarbrücken, Germany
Simionato, Greta; Department of Experimental Physics, Saarland University, 66123 Saarbrücken, Germany ; Department of Experimental Surgery, Campus University Hospital, Saarland University, 66421 Homburg, Germany
Qiao, Min ; Theoretical Medicine and Biosciences, Campus University Hospital, Saarland University, 66421 Homburg, Germany ; Department of Experimental Physics, Saarland University, 66123 Saarbrücken, Germany
Van der Zwaan, Carmen; Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands ; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1007 MB Amsterdam, The Netherlands
Rotordam, Maria Giustina; Nanion Technologies, 80339 Munich, Germany
John, Thomas ; Department of Experimental Physics, Saarland University, 66123 Saarbrücken, Germany
Hertz, Laura; Theoretical Medicine and Biosciences, Campus University Hospital, Saarland University, 66421 Homburg, Germany ; Department of Experimental Physics, Saarland University, 66123 Saarbrücken, Germany
Hoogendijk, Arjan J; Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands ; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1007 MB Amsterdam, The Netherlands
WAGNER, Christian ; University of Luxembourg ; Department of Experimental Physics, Saarland University, 66123 Saarbrücken, Germany
Von Lindern, Marieke ; Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands ; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1007 MB Amsterdam, The Netherlands
Egee, Stephane ; Biological Station Roscoff, Sorbonne University, CNRS, UMR8227 LBI2M, F-29680 Roscoff, France ; Laboratory of Excellence GR-Ex, F-75015 Paris, France
Van den Akker, Emile ; Department of Hematopoiesis, Sanquin Research, 1066 CX Amsterdam, The Netherlands ; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1007 MB Amsterdam, The Netherlands
Kaestner, Lars ; Theoretical Medicine and Biosciences, Campus University Hospital, Saarland University, 66421 Homburg, Germany ; Department of Experimental Physics, Saarland University, 66123 Saarbrücken, Germany
The three authors (Nicoletta Murciano, Maria Giustina Rotordam and Nadine Becker) are employees of Nanion, work was performed with funding from the European Community (see above). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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