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Topic Review
cAMP-Related Macromolecular Complexes Regulating CFTR Opening
Cystic fibrosis (CF) is the rare genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These molecules, known as CFTR modulators, have led to unprecedented improvements in the lung function and quality of life of most CF patients. However, the efficacy of these drugs is still suboptimal, and the clinical response is highly variable even among individuals bearing the same mutation. Furthermore, not all patients carrying rare CFTR mutations are eligible for CFTR modulator therapies, indicating the need for alternative and/or add-on therapeutic approaches. Because the second messenger 3′,5′-cyclic adenosine monophosphate (cAMP) represents the primary trigger for CFTR activation and a major regulator of different steps of the life cycle of the channel, there is growing interest in devising ways to fine-tune the cAMP signaling pathway for therapeutic purposes.
  • 345
  • 07 Jul 2023
Topic Review
Caloric Restriction
Caloric restriction (CR) is a traditional but scientifically verified approach to promoting health and increasing lifespan. CR exerts its effects through multiple molecular pathways that trigger major metabolic adaptations. It influences key nutrient and energy-sensing pathways including mammalian target of rapamycin, Sirtuin 1, AMP-activated protein kinase, and insulin signaling, ultimately resulting in reductions in basic metabolic rate, inflammation, and oxidative stress, as well as increased autophagy and mitochondrial efficiency.
  • 722
  • 27 Oct 2020
Topic Review
Calmodulin-Connexin in Gap Junction Channel Regulation-Calmodulin-Cork Gating Model
In the past four decades numerous findings have indicated that gap junction channel gating is mediated by intracellular calcium concentrations ([Ca2+i]) in the high nanomolar range via calmodulin (CaM). We believe that CaM directly closes the channel by a cork-like gating mechanism.
  • 611
  • 16 Dec 2021
Topic Review
Calmodulin Interactions with Voltage-Gated Sodium-Channels
Calmodulin (CaM) is a small protein that acts as a ubiquitous signal transducer and regulates neuronal plasticity, muscle contraction, and immune response. It interacts with ion channels and plays regulatory roles in cellular electrophysiology. CaM modulates the voltage-gated sodium channel gating process, alters sodium current density, and regulates sodium channel protein trafficking and expression.
  • 786
  • 24 Sep 2021
Topic Review
Calebin A, a Compound of Turmeric
Calebin A (CA) is one of the active constituents of turmeric and has anti-inflammatory and antioxidant effects. Excessive inflammation and cell apoptosis are the main causes of tendinitis and tendinopathies. However, the role of CA in tendinitis is still unclear and needs to be studied in detail.
  • 399
  • 29 Mar 2022
Topic Review
Calcium Sources to Somatic Release of Serotonin
The soma, dendrites and axon of neurons may display calcium-dependent release of transmitters and peptides. Such release is named extrasynaptic for occurring in absence of synaptic structures. Emphasis is given to the somatic release of serotonin by the classical leech Retzius neuron, which has allowed detailed studies on the fine steps from excitation to exocytosis. Trains of action potentials induce transmembrane calcium entry through L-type channels. For action potential frequencies above 5 Hz, summation of calcium transients on individual action potentials activates the second calcium source: ryanodine receptors produce calcium-induced calcium release. The resulting calcium tsunami activates mitochondrial ATP synthesis to fuel transport of vesicles to the plasma membrane. Serotonin that is released maintains a large-scale exocytosis by activating the third calcium source: serotonin autoreceptors coupled to phospholipase C promote IP3 production. Activated IP3 receptors in peripheral endoplasmic reticulum release calcium that promotes vesicle fusion. The Swiss-clock workings of the machinery for somatic exocytosis has a striking disadvantage. The essential calcium-releasing endoplasmic reticulum near the plasma membrane hinders the vesicle transport, drastically reducing the thermodynamic efficiency of the ATP expenses and elevating the energy cost of release. 
  • 615
  • 09 Feb 2022
Topic Review
Calcium Signaling Regulates Autophagy
Calcium (Ca2+) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca2+ channels and Ca2+ storage in various organelles is critical in maintaining cytosolic Ca2+ levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca2+ homeostasis is a store-operated Ca2+ entry (SOCE) mechanism that is activated by the depletion of Ca2+ from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells.
  • 471
  • 08 Oct 2021
Topic Review
Calcium Signaling of Heat Shock in Crop Plants
Climate change and the increasing frequency of high temperature (HT) events are significant threats to global crop yields. To address this, a comprehensive understanding of how plants respond to heat shock (HS) is essential. Signaling pathways involving calcium (Ca2+), a versatile second messenger in plants, encode information through temporal and spatial variations in ion concentration. Ca2+ is detected by Ca2+-sensing effectors, including channels and binding proteins, which trigger specific cellular responses. At elevated temperatures, the cytosolic concentration of Ca2+ in plant cells increases rapidly, making Ca2+ signals the earliest response to HS. 
  • 185
  • 17 Jan 2024
Topic Review
Calcium Signaling and Mitochondrial Oxidative Capacity
The intermyofibrillar mitochondria constitute the majority of the three-mitochondrial subpopulations in the cardiac myocyte. They are also considered to be the most important in terms of their ability to participate in calcium and cellular signaling, which are critical for the regulation of mitochondrial function and adenosine triphosphate (ATP) production. 
  • 688
  • 20 Oct 2021
Topic Review
Calcium in Apoptosis and Cancer
Calcium (Ca2+) is a major second messenger in cells and is essential for the fate and survival of all higher organisms. Different Ca2+ channels, pumps, or exchangers regulate variations in the duration and levels of intracellular Ca2+, which may be transient or sustained. These changes are then decoded by an elaborate toolkit of Ca2+-sensors, which translate Ca2+ signal to intracellular operational cell machinery, thereby regulating numerous Ca2+-dependent physiological processes. Alterations to Ca2+ homoeostasis and signaling are often deleterious and are associated with certain pathological states, including cancer. Altered Ca2+ transmission has been implicated in a variety of processes fundamental for the uncontrolled proliferation and invasiveness of tumor cells and other processes important for cancer progression, such as the development of resistance to cancer therapies.
  • 725
  • 22 Sep 2021
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