A value of Ca2+ binding in 1 second by sarcoplasmic reticulum fragments from guinea pig hearts increased proportionally to elevation of Ca2+ concentration from 0.1 to 3.0(-6) M at pH 7.2. Decline of pH to 6.8 and 6.2 decreased the Ca2+ bound in 1 second, but increased the Ca2+ bound in 30 seconds when membrane permeability has become a crucial factor in determining Ca2+ bound. In experiments on guinea pig papillary muscles, a decline of pH from 7.35 to 6.83 resulted in a nearly equal fall in velocities of isometric contraction and relaxation (27 and 21%, respectively), but during isotonic shortening when the relaxation proceeds much faster, a fall in relaxation velocity (44 +/- 3%) was significantly more profound as compared to the fall in contraction velocity (29 +/- 4%). This effect as well as a decrease in initial rate of Ca2+ binding by sarcoplasmic reticulum suggest a direct inhibitory effect of acidosis on Ca2+ removal from myofibrils in myocardial cells.
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Nature
January 2025
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA.
The γ-carboxylation of glutamate residues enables Ca-mediated membrane assembly of protein complexes that support broad physiological functions including hemostasis, calcium homeostasis, immune response, and endocrine regulation. Modulating γ-carboxylation level provides prevalent treatments for hemorrhagic and thromboembolic diseases. This unique posttranslational modification requires vitamin K hydroquinone (KH) to drive highly demanding reactions catalyzed by the membrane-integrated γ-carboxylase (VKGC).
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January 2025
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
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School of Computer Science and Technology, Baotou Medical College, Baotou, China.
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View Article and Find Full Text PDFFront Cardiovasc Med
January 2025
Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China.
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View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Department of Physiology and Membrane Biology, University of California Davis, Davis, CA 95616.
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