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The cytoplasmic free Ca2+ concentration ([Ca2+]i) is a key determinant of neuronal information transfer and processing. It controls a plethora of fundamental processes, including transmitter release and the induction of synaptic plasticity. This enigmatic second messenger conveys its wide variety of actions by binding to a subgroup of Ca2+ binding proteins (CaBPs) known as “Ca2+ sensors”. Well known examples of Ca2+ sensors are Troponin-C in skeletal muscle, Synaptotagmin in presynaptic terminals, and Calmodulin (CaM) in all eukaryotic cells. Since the levels of [Ca2+]i directly influence the potency of Ca2+ sensors, the Ca2+ concentration is tightly controlled by several mechanisms including another type of Ca2+ binding proteins, the Ca2+ buffers. Prominent examples of Ca2+ buffers include Parvalbumin (PV), Calbindin-D28k (CB) and Calretinin (CR), although for the latter two Ca2+ sensor functions were recently also suggested. Ca2+ buffers are distinct from sensors by their purely buffering action, i.e. they influence the spatio-temporal extent of Ca2+ signals, without directly binding downstream target proteins. Details of their action depend on their binding kinetics, mobility, and concentration. Thus, neurons can control the range of action of Ca2+ by the type and concentration of CaBPs expressed. Since buffering strongly limits the range of action of free Ca2+, the structure of the Ca2+ signaling domain and the topographical relationships between the sites of Ca2+ influx and the location of the Ca2+ sensors are central determinants in neuronal information processing. For example, postsynaptic dendritic spines act to compartmentalize Ca2+ depending on their geometry and expression of CaBPs, thereby influencing dendritic integration. At presynaptic sites it has been shown that tight, so called nanodomain coupling between Ca2+ channels and the sensor for vesicular transmitter release increases speed and reliability of synaptic transmission. Vice versa, the influence of an individual CaBP on information processing depends on the topographical relationships within the signaling domain. If e.g. source and sensor are very close, only buffers with rapid binding kinetics can interfere with signaling. This Research Topic contains a collection of work dealing with the relationships between different [Ca2+]i controlling mechanisms in the structural context of synaptic sites and their functional implications for synaptic information processing as detailed in the Editorial.
Calcium --- localization --- calcium sensor --- calcium buffer --- transmitter release --- plasticity --- dendritic integration --- storm --- STED
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The calcium-calmodulin dependent protein kinases (CaMKs) are a broadly expressed family of calcium-sensitive intracellular kinases, which are responsible for transducing cytosolic calcium signals into phosphorylation-based regulation of proteins and physiological functions. As the multifunctional member of the family, CaMKII has become the most prominent for its roles in the central nervous system and heart, where it controls a diverse range of calcium-dependent processes; from learning and memory at the neuronal synapse, to cellular growth and death in the myocardium. In the heart, CaMKII directly regulates many of the most important ion channels and calcium handling proteins, and controls the expression of an ever-increasing number of transcripts and their downstream products. Functionally, these actions are thought to orchestrate many of the electrophysiologic and contractile adaptations to common cardiac stressors, such as rapid pacing, chronic adrenergic stimulation, and oxidative challenge. In the context of disease, CaMKII has been shown to contribute to a remarkably wide variety of cardiac pathologies, of which heart failure (HF) is the most conspicuous. Hyperactivity of CaMKII is an established contributor to pathological cardiac remodeling, and is widely thought to directly promote arrhythmia and contractile dysfunction during HF. Moreover, several non-failing arrhythmia-susceptible phenotypes, which result from specific genetic channelopathies, functionally mimic constitutive channel phosphorylation by CaMKII. Because CaMKII contributes to both the acute and chronic manifestations of major cardiac diseases, but may be only minimally required for homeostasis in the absence of chronic stress, it has come to be one of the most promising therapeutic drug targets in cardiac biology. Thus, development of more specific and deliverable small molecule antagonists remains a key priority for the field. Here we provide a selection of articles to summarize the state of our knowledge regarding CaMKII in cardiac health and disease, with a particular view to highlighting recent developments in CaMKII activation, and new targets in CaMKII-mediated control of myocyte physiology.
Heart Failure --- Hypertrophy --- arrhythmia --- Ion Channels --- Phosphorylation --- Calcium
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Each one of us in his life has, at least once, smelled the scent of roses, read one canto of Dante’s Commedia or listened to the sound of the sea from a shell. All of this is possible thanks to the astonishing capabilities of an organ, such as the brain, that allows us to collect and organize perceptions coming from sensory organs and to produce behavioural responses accordingly. Studying an operating brain in a non-invasive way is extremely difficult in mammals, and particularly in humans. In the last decade, a small teleost fish, zebrafish (Danio rerio), has been making its way into the field of neurosciences. The brain of a larval zebrafish is made up of 'only' 100000 neurons and it’s completely transparent, making it possible to optically access it. Here, taking advantage of the best of currently available technology, we devised optical solutions to investigate the dynamics of neuronal activity throughout the entire brain of zebrafish larvae.
zebrafish --- calcium imaging --- light-sheet microscopy --- epilepsy --- behaviour
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It is in general well appreciated that the cortical interneurons play various important roles in cortical neuronal networks both in normal and pathological states. Based on connectivity pattern, developmental, morphological and electrophysiological properties, distinct subgroups of GABAergic interneurons can be differentiated in the neocortex as well as in the hippocampal formation. In this E-Book, we are focusing our attention on inhibitory interneurons expressing calcium-binding protein calretinin (CR). The aim of the E-Book is to consolidate the knowledge about this interneuronal population and to inspire further research on the function and malfunction of these neurons, which – functionally – seem to stand "at the top of the pyramid" of cortical interneuronal types.
calretinin --- Interneurons --- Cortical Circuits --- Cortical development --- GABA --- Calcium-Binding Proteins --- Epilepsy --- claustrum --- Hippocampus --- Neocortex
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Maxi calcium-activated potassium channels (BK) are an amazing category of ion channels which are found in cellular plasma membranes as well as in membranes of intracellular organelles. The function of these channels is to repolarize any excited membrane by passing a potassium outward current, in response to depolarization and/or increase in local calcium levels. Thus, voltage and calcium ions are involved in gating the channel under physiological conditions. This dual activation makes them perfect sensors for many cellular events that require integration between intracellular calcium levels and electrical signals. A plethora of physiological and pathophysiological functions, such as membrane hyperpolarization, modulation of synaptic transmission, hormone secretion or mental deficiencies, vaso-regulation, epilepsies, heart diseases, myotonic dystrophies, hypertension etc, in almost all cells and tissues were reported for these channels. BK channels are main targets for important ligands like alcohol and gaseous neurotransmitters, such as NO, CO or H2S, to name a few. In the last years, the molecular entities and mechanisms involved in modulation of BK channels have gained tremendous attention, as the key role of these channels in cellular processes became increasingly recognized. Indeed, accessory proteins such as slob, beta and gamma subunits, all serve to modulate the channel gating characteristics. Moreover, channel subunit expression and function is further tuned by phosphorylation/ dephosphorylation processes, redox mechanisms and the lipid microenvironment of the BK channel protein complex. This e-book contains structural and functional aspects of BK channels, channel modulation by a variety of agents and cellular components, as well as the channel’s relevance in health and disease.
BK channel --- Slo --- health --- disease --- ethanol --- nervous system --- hydrogensulfide --- maxi calcium activated potassium channel --- KCNMA1 --- ischemia
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Plants use the Sun's energy to synthesize the basic biomolecules that make up all the organic matter of all organisms of terrestrial ecosystems, including ourselves. Therefore, understanding their adaptive mechanisms to variations of environmental factors, both biotic and abiotic, is fundamental, and particularly relevant in the current context of rapid climate change. Some of the most important adaptive mechanisms of plants are the electrical and chemical signaling systems for the exchange of information between proximally and distally located cells. These signalling systems allow plants to dynamically coordinate the activities of all cells under a diversity of situations. In this Research Topic, we present eight articles that bring up new hypothesis and data to understand the mechanisms of systemic electrical signaling and the central role that it plays in adapting the whole plant to different stresses, as well as new findings on intracellular calcium and nitric oxide-based signaling pathways under stress, which could be extrapolated to non-plant research.
plant electrophysiology --- ion channels --- intracellular calcium --- nitric oxide --- circumnutation --- phloem --- photosynthesis --- environmental stress --- action potential --- Arabidopsis
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Features of Ca2+ signals including the amplitude, duration, frequency and location are encoded by various physiological stimuli. These features of the signals are decoded by cells to selectively activate smooth muscle functions that include contraction and proliferation [1–3]. Central, therefore, to an appreciation of how smooth muscle is controlled is an understanding of the regulation of Ca2+.
Mitochondria structure and position --- local control --- calcium signals --- smooth muscle cells
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The tale of cyclic GMP has been astonishing. Having overcome an initial disbelief, cyclic GMP has risen to its present eminence as a premium cellular signal transduction messenger of not only hormonal extracellular but also of the intracellular signals. This research topic focuses on the pathways and functions of membrane guanylate cyclases in different tissues of the body and their interplay with intracellular sensory signals where in many cases, cyclic GMP along with Ca2+ have taken on roles as synarchic co-messengers.
membrane guanylate cyclase --- Cyclic GMP --- Calcium --- ANF-RGC --- ROS-GC --- synaptic plasticity --- Gene Therapy --- Visceral Pain --- trafficking --- Glaucoma
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Genetically encoded indicators emerged as promising tools for cell type-specific and chronic recording of neuronal population activity. Since publication of the first prototypical genetically encoded Ca2+ indicators (Cameleons) in 1997, we have witnessed remarkable evolution of the field, with rapid improvement of indicator performance as well as expanded application to many model organisms in the neuroscience community. Challenges still remain, however, concerning the mammalian central nervous system: limited sensitivity of indicators to subtle changes in activity, slow signal kinetics, cytotoxicity after a long-term and high-level expression of indicators, and variable performance across cell types. In addition to improvement of the indicators per se, development of strategies that allow combined use of the indicators and optogenetic tools is also desired. In this Research Topic, we recruited top researchers in the field and their young colleagues to present their cutting-edge research as well as insightful opinions on the following subtopics:1) Latest breakthroughs on development of genetically encoded indicators2) Novel scientific findings obtained with genetically encoded indicators3) Wishlist for the next-generation genetically encoded indicators4) Guideline for selecting an appropriate indicator5) Optimal methodology for indicator delivery to mammalian CNS
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This Special Issue is aimed at presenting the state of the art of the multidisciplinary science concerning all aspects of volcanic plumes, of relevance to the volcanology, climatology, atmospheric science, and remote sensing communities.
calcium carbonate --- crystallization --- hydrogels --- alginate --- xanthan --- SEM --- X-ray diffraction --- carbonation --- micromechanics --- CaCO3 --- cement --- ammonia bicarbonate --- carbon dioxide --- mass-transfer coefficient --- capture --- bubble-column scrubber --- calcium carbonate --- alginate --- Lessonia nigrescens --- electrocrystallization --- multi-wall carbon nanotubes --- potentiometric titration --- calcium carbonate --- phosphorylated chitin --- electrocrystallization --- potentiometric titration --- gas diffusion method --- sedimentary model --- Callovian-Oxfordian --- Amu Darya Basin --- reservoir --- main controlling factors --- MICP --- Sporosarcina pasteurii --- Bacillus subtilis --- bacterial extracellular secretion --- urease --- calcite --- contact angle --- surface energy --- biomineralization --- calcite --- aragonite --- sericin --- nacre --- CO2 --- composite --- hierarchic structure
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