Maren Schulz
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Maren Schulz has a total of 7 co-authors. Here are the top co-authors by number of shared publications:
- Andreas Leffler
Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, Hannover, Germany
1 shared publication - Christine Herzog
Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, Germany
1 shared publication - Daniel Rudolf
Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, Germany
1 shared publication - Frank Götz Echtermeyer
Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, Germany
1 shared publication - Inês Carvalheira Arnaut Pombeiro Stein
Department of Anesthesiology and Intensive Care Medicine, Hannover Medical School, 30625 Hannover, Germany
1 shared publication - Nils Kriedemann
Leibniz Research Laboratories for Biotechnology and Artificial Organs, Department of Cardiothoracic Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany
1 shared publication
Latest Publications
- Open Access
Weak Acids as Endogenous Inhibitors of the Proton-Activated Chloride Channel
The recently identified proton-activated chloride (PAC) channel is ubiquitously expressed, and it regulates several proton-sensitive physiological and pathophysiological processes. While the PAC channel is activated by strong acids due to the binding of protons to extracellular binding sites, here, we describe the way in which weak acids inhibit the PAC channel by a mechanism involving a distinct extracellular binding site. Whole-cell patch clamp was performed on wildtype HEK293T cells, PAC-knockout HEK293 cells expressing human (h)PAC mutant constructs, and on hiPSC-derived cardiomyocytes. Proton-induced cytotoxicity was examined in HEK293T cells. Acetic acid inhibited endogenous PAC channels in HEK 293T cells in a reversible, concentration-dependent, and pH-dependent manner. The inhibition of PAC channels was also induced by lactic acid, propionic acid, itaconic acid, and β-hydroxybutyrate. Weak acids also inhibited recombinant wildtype hPAC channels and PAC-like currents in hiPSC-derived cardiomyocytes. Replacement of the extracellular arginine 93 by an alanine (hPAC–Arg93Ala) strongly reduced the inhibition by some weak acids, including arachidonic acid. Although lactic acid inhibited PAC, it did not reduce the proton-induced cytotoxicity examined in wildtype HEK 293 cells. To conclude, weak acids inhibit PAC via an extracellular mechanism involving Arg93. These data warrant further investigations into the regulation of the PAC channel by endogenous weak acids.
Open AccessWeak Acids as Endogenous Inhibitors of the Proton-Activated Chloride Channel
The recently identified proton-activated chloride (PAC) channel is ubiquitously expressed, and it regulates several proton-sensitive physiological and pathophysiological processes. While the PAC channel is activated by strong acids due to the binding of protons to extracellular binding sites, here, we describe the way in which weak acids inhibit the PAC channel by a mechanism involving a distinct extracellular binding site. Whole-cell patch clamp was performed on wildtype HEK293T cells, PAC-knockout HEK293 cells expressing human (h)PAC mutant constructs, and on hiPSC-derived cardiomyocytes. Proton-induced cytotoxicity was examined in HEK293T cells. Acetic acid inhibited endogenous PAC channels in HEK 293T cells in a reversible, concentration-dependent, and pH-dependent manner. The inhibition of PAC channels was also induced by lactic acid, propionic acid, itaconic acid, and β-hydroxybutyrate. Weak acids also inhibited recombinant wildtype hPAC channels and PAC-like currents in hiPSC-derived cardiomyocytes. Replacement of the extracellular arginine 93 by an alanine (hPAC–Arg93Ala) strongly reduced the inhibition by some weak acids, including arachidonic acid. Although lactic acid inhibited PAC, it did not reduce the proton-induced cytotoxicity examined in wildtype HEK 293 cells. To conclude, weak acids inhibit PAC via an extracellular mechanism involving Arg93. These data warrant further investigations into the regulation of the PAC channel by endogenous weak acids.