Sarcoplasmic reticulum (SR) membranes from rabbit muscle were deposited on silicon substrates and characterized by the combination of spectral ellipsometry (SE), high energy specular X-ray reflectivity (XRR), specular neutron reflectivity (NR), and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Following the optimization of the preparative conditions by SE, the detailed structures in the direction perpendicular to the membrane were probed by XRR. ATR-FTIR data showed strong signals from amide I and amide II bands of the native SR membranes containing a large amount of Ca-ATPase, which could not be achieved by the reconstitution in artificial lipid membranes. The treatment with protease led to a significant decrease in the amide peaks, and the XRR data confirmed the modulation of the membrane structures. The obtained data show the potential of the in situ combination of reflectivity and vibrational spectroscopy of native supported membranes in order to unravel both structure and dynamics of complex biological membranes.
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http://dx.doi.org/10.1021/acs.langmuir.4c02691 | DOI Listing |
Int J Mol Sci
December 2024
Institute of Molecular Physiology and Genetics, Centre of Biosciences, Slovak Academy of Sciences, Dubravska cesta 9, 840 05 Bratislava, Slovakia.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly arrhythmogenic syndrome triggered by stress, primarily linked to gain-of-function point mutations in the cardiac ryanodine receptor (RyR2). Flecainide, as an effective therapy for CPVT, is a known blocker of the surface-membrane Na channel, also affecting the intracellular RyR2 channel. The therapeutic relevance of the flecainide-RyR2 interaction remains controversial, as flecainide blocks only the RyR2 current flowing in the opposite direction to the physiological Ca release from the sarcoplasmic reticulum (SR).
View Article and Find Full Text PDFCells
December 2024
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institute of Health, Baltimore, MD 21224, USA.
The spontaneous firing of the sinoatrial (SA) node, the physiological pacemaker of the heart, is generated within sinoatrial nodal cells (SANCs) and is regulated by a "coupled-clock" pacemaker system, which integrates a "membrane clock", the ensemble of ion channel currents, and an intracellular "Ca clock", sarcoplasmic reticulum-generated local submembrane Ca releases via ryanodine receptors. The interactions within a "coupled-clock" system are modulated by phosphorylation of surface membrane and sarcoplasmic reticulum proteins. Though the essential role of a high basal cAMP level and PKA-dependent phosphorylation for basal spontaneous SANC firing is well recognized, the role of basal CaMKII-dependent phosphorylation remains uncertain.
View Article and Find Full Text PDFCurr Probl Cardiol
January 2025
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
The regulation of calcium signaling within cardiomyocytes is pivotal for maintaining cardiac function, with disruptions in sarcoplasmic reticulum (SR) calcium handling linked to various heart diseases. This review explores the emerging role of microRNAs (miRNAs) in modulating SR calcium dynamics, highlighting their influence on cardiomyocyte maturation, function, and disease progression. We present a comprehensive overview of the mechanisms by which specific miRNAs, such as miR-1, miR-24, and miR-22, regulate key components of calcium handling, including ryanodine receptors, SERCA, and NCX.
View Article and Find Full Text PDFToxicol Appl Pharmacol
January 2025
Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, South Korea. Electronic address:
This study explored the vasodilatory mechanisms of the sodium-glucose cotransporter-2 inhibitor remogliflozin using femoral arteries of rabbits. Remogliflozin dilated femoral arterial rings pre-contracted with phenylephrine in a concentration-dependent manner. Pretreatment with the Ca-sensitive K channel inhibitor (paxilline), the ATP-sensitive K channel inhibitor (glibenclamide), or the inwardly rectifying K channel inhibitor (Ba) did not alter the vasodilatory effect.
View Article and Find Full Text PDFJ Inorg Biochem
December 2024
Rutgers, The State University of New Jersey, Dept of Pharmacology, Physiology & Neuroscience, Newark, NJ, United States of America.
Crown ethers have been shown to have physiological effects ascribed to their ionophoric properties. However, high levels of toxicity precluded interest in their evaluation as therapeutic agents. We prepared new silacrown analogs of crown ethers.
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