The intracellular Ca(2+)-homeostasis may be affected by changes of the extracellular K(+)- and/or Mg(2+)-concentrations. Mg2+ reduces the Ca(2+)-influx via L-type Ca(2+)-channels, facilitates Ca(2+)-uptake into the sarcoplasmic reticulum, modulates the Ca(2+)-induced Ca(2+)-release and the Ca(2+)-binding to troponin C. The extracellular K+ activates the Na+/K(+)-ATPase and changes the membrane potential thereby affecting the mode of action of the Na+/Ca(2+)-exchanger. Especially when intracellular Ca2+ regulation is altered, for example in heart failure, Mg2+ and K+ exert beneficial effects on the frequency-dependent force-generation in human myocardium. Thus, extracellular Mg2+ and K+ influence contraction coupling in the human myocardium.
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http://dx.doi.org/10.1007/BF03042651 | DOI Listing |
J Am Chem Soc
January 2025
State Key Laboratory of Molecular Reaction Dynamics, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Directly probing the heterogeneous conformations of intracellular proteins within their native cellular environment remains a significant challenge in mass spectrometry (MS). Here, we establish an in-cell MS and ultraviolet photodissociation (UVPD) strategy that directly ejects proteins from living cells into a mass spectrometer, followed by 193 nm UVPD for structural analysis. Applying this approach to calmodulin (CaM), we reveal that it adopts more extended conformations within living cells compared with purified samples , highlighting the unique influence of intracellular environments on protein folding.
View Article and Find Full Text PDFJ Gen Physiol
March 2025
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Voltage-gated Ca2+ channels (VGCCs) are highly expressed throughout numerous biological systems and play critical roles in synaptic transmission, cardiac excitation, and muscle contraction. To perform these various functions, VGCCs are highly regulated. Inactivation comprises a critical mechanism controlling the entry of Ca2+ through these channels and constitutes an important means to regulate cellular excitability, shape action potentials, control intracellular Ca2+ levels, and contribute to long-term potentiation and depression.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, China.
In patients with acute myocardial infarction (AMI), thrombolytic therapy and revascularization strategies allow complete recanalization of occluded epicardial coronary arteries. However, approximately 35% of patients still experience myocardial ischemia/reperfusion (I/R) injury, which contributing to increased AMI mortality. Therefore, an accurate understanding of myocardial I/R injury is important for preventing and treating AMI.
View Article and Find Full Text PDFBiochem Soc Trans
January 2025
Departamento de Ciencias Médicas Básicas, Facultad de Ciencias de la Salud-sección Medicina, Universidad de La Laguna, Tenerife, ES-38071, Spain.
Large conductance voltage- and calcium-activated potassium channels (BK channels) are extensively found throughout the central nervous system and play a crucial role in various neuronal functions. These channels are activated by a combination of cell membrane depolarisation and an increase in intracellular calcium concentration, provided by calcium sources located close to BK. In 2001, Isaacson and Murphy first demonstrated the coupling of BK channels with N-methyl-D-aspartate receptors (NMDAR) in olfactory bulb neurons.
View Article and Find Full Text PDFNat Rev Mol Cell Biol
January 2025
MitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
Activation of Ca channels in Ca stores in organelles and the plasma membrane generates cytoplasmic calcium ([Ca]) signals that control almost every aspect of cell function, including metabolism, vesicle fusion and contraction. Mitochondria have a high capacity for Ca uptake and chelation, alongside efficient Ca release mechanisms. Still, mitochondria do not store Ca in a prolonged manner under physiological conditions and lack the capacity to generate global [Ca] signals.
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