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Ion channels are membrane proteins that selectively allow ions to flow down their electrochemical gradient across the cellular membrane. They localize in both plasma and intracellular membranes and regulate a variety of functions such as neuronal excitability, heartbeat, muscle contraction and hormones release. Thus, understanding the molecular mechanism of ion channels function and regulation is one of the key goals of modern Biophysics. During my PhD thesis, by combining patch-clamp measurements with site-direct mutagenesis, fluorophore labeling experiments and pharmacological assays, I explored some functional and structural properties of different ion transporters: the Na+/Ca2+ exchanger (NCX); the large conductance Ca2+-voltage activated K+ channel (BK) channel; the human Transient receptor potential, member A1 (TRPA1) channel.

Patch-clamp techniques (Electrophysiology) --- Ion channels.

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Ion channels are membrane proteins that selectively allow ions to flow down their electrochemical gradient across the cellular membrane. They localize in both plasma and intracellular membranes and regulate a variety of functions such as neuronal excitability, heartbeat, muscle contraction and hormones release. Thus, understanding the molecular mechanism of ion channels function and regulation is one of the key goals of modern Biophysics. During my PhD thesis, by combining patch-clamp measurements with site-direct mutagenesis, fluorophore labeling experiments and pharmacological assays, I explored some functional and structural properties of different ion transporters: the Na+/Ca2+ exchanger (NCX); the large conductance Ca2+-voltage activated K+ channel (BK) channel; the human Transient receptor potential, member A1 (TRPA1) channel.

Ion channels. --- Patch-clamp techniques (Electrophysiology)

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This book brings together leading international experts to discuss recent advances in the regulation of presynaptic voltage-gated Ca2+ channels (VGCCs), key signal transducers that represent one of the most widely modulated proteins in the body. It is now commonly accepted that presence of the VGCC complex defines an excitable cell. At a basic level, VGCCs transduce membrane potential change to chemical neurotransmitter release at presynaptic terminals. However, on-going scientific research, presented here, in areas including neuroscience, electrophysiology, pharmacology, biochemistry and, increasingly, proteomics, has revealed the widespread nature of modulation of the presynaptic VGCC complex. This book reviews and discusses the following topics: The fundamental role of the VGCC pore-forming CaVa subunit, and some of their binding partners, in presynaptic function and synaptic plasticity. Modulation of presynaptic CaVa subunits by auxiliary CaVb and a2d subunits and by their major interaction partners, such as active zone scaffolding proteins, synaptic proteins, G proteins and small GTPases, which, together, contribute to the VGCC proteome. Work at the cutting edge of research, including how direct electrophysiology recordings from presynaptic terminals and introduction of synthetic CaVa peptides into presynaptic terminals has expanded our knowledge of VGCC function. Evidence emerging over the last decade demonstrating that VGCC subunits represent bona fide molecular targets for therapeutic drug discovery. This development is illustrated by the introduction of the CaV2.2 blocker ziconotide, which represents an important proof-of-concept, but is best exemplified by the emergence of gabapentinoids, which bind the VGCC auxiliary a2d subunit, as first-line treatments for chronic neuropathic pain. Throughout, chapters are accompanied with illustrative Tables and Figure providing a useful and comprehensive summary of the current state-of-play in this area of significant therapeutic interest. Work described here also provides a solid basis for future research in this important area.

Calcium -- Physiological effect. --- Calcium channels. --- Calcium. --- Presynaptic receptors. --- Ion Channels --- Electrophysiological Processes --- Nervous System Physiological Processes --- Intercellular Junctions --- Axons --- Signal Transduction --- Nervous System --- Physiological Processes --- Membrane Glycoproteins --- Biochemical Processes --- Membrane Transport Proteins --- Nervous System Physiological Phenomena --- Cell Physiological Processes --- Electrophysiological Phenomena --- Neurons --- Nerve Fibers --- Cell Membrane Structures --- Anatomy --- Cell Membrane --- Biochemical Phenomena --- Membrane Proteins --- Physiological Phenomena --- Carrier Proteins --- Cells --- Musculoskeletal and Neural Physiological Phenomena --- Chemical Processes --- Cell Physiological Phenomena --- Proteins --- Chemical Phenomena --- Phenomena and Processes --- Cellular Structures --- Amino Acids, Peptides, and Proteins --- Chemicals and Drugs --- Neuronal Plasticity --- Synaptic Transmission --- Synapses --- Presynaptic Terminals --- Calcium Channels --- Calcium in the body. --- Channels, Calcium --- Medicine. --- Cell physiology. --- Cell membranes. --- Neurobiology. --- Biomedicine. --- Biomedicine general. --- Membrane Biology. --- Cell Physiology. --- Body composition --- Calcification --- Ion channels --- Cell function --- Cytology --- Physiology --- Cell surfaces --- Cytoplasmic membranes --- Plasma membranes --- Plasmalemma --- Membranes (Biology) --- Glycocalyces --- Neurosciences --- Clinical sciences --- Medical profession --- Human biology --- Life sciences --- Medical sciences --- Pathology --- Physicians --- Biomedicine, general. --- Health Workforce --- Cell membranes .

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In recent years, the fabrication of nanomaterials and exploration of their properties have attracted the attention of various scientific disciplines such as biology, physics, chemistry, and engineering. Although nanoparticulate systems are of significant interest in various scientific and technological areas, there is little known about the safety of these nanoscale objects. It has now been established that the surfaces of nanoparticles are immediately covered by biomolecules (e.g. proteins, ions, and enzymes) upon their entrance into a biological medium. This interaction with the biological medium modulates the surface of the nanoparticles, conferring a “biological identity” to their surfaces (referred to as a “corona”), which determines the subsequent cellular/tissue responses. The new interface between the nanoparticles and the biological medium/proteins, called “bio-nano interface,” has been very rarely studied in detail to date, though the interest in this topic is rapidly growing. In this book, the importance of the physiochemical characteristics of nanoparticles for the properties of the protein corona is discussed in detail, followed by comprehensive descriptions of the methods for assessing the protein-nanoparticle interactions. The advantages and limitations of available corona evaluation methods (e.g. spectroscopy methods, mass spectrometry, nuclear magnetic resonance, electron microscopy, X-ray crystallography, and differential centrifugal sedimentation) are examined in detail, followed by a discussion of the possibilities for enhancing the current methods and a call for new techniques. Moreover, the advantages and disadvantages of protein-nanoparticle interaction phenomena are explored and discussed, with a focus on the biological impacts.

Biotechnology. --- Ion channels. --- Membranes (Biology). --- Nanotechnology. --- Nanobiotechnology --- Nanostructured materials --- Proteins --- Nanostructures --- Natural Science Disciplines --- Physicochemical Phenomena --- Amino Acids, Peptides, and Proteins --- Disciplines and Occupations --- Manufactured Materials --- Chemical Phenomena --- Chemicals and Drugs --- Technology, Industry, and Agriculture --- Phenomena and Processes --- Technology, Industry, Agriculture --- Chemistry --- Surface Properties --- Nanoparticles --- Biology --- Health & Biological Sciences --- Physical Sciences & Mathematics --- Biochemistry --- Biology - General --- Nanostructured materials. --- Molecular technology --- Nanoscale technology --- Nanomaterials --- Nanometer materials --- Nanophase materials --- Nanostructure controlled materials --- Nanostructure materials --- Ultra-fine microstructure materials --- Life sciences. --- Pharmacology. --- Biochemistry. --- Proteins. --- Nanoscale science. --- Nanoscience. --- Nanostructures. --- Biophysics. --- Biological physics. --- Life Sciences. --- Biochemistry, general. --- Protein-Ligand Interactions. --- Pharmacology/Toxicology. --- Biophysics and Biological Physics. --- Nanoscale Science and Technology. --- High technology --- Microstructure --- Nanotechnology --- RNA-ligand interactions. --- Toxicology. --- Biological and Medical Physics, Biophysics. --- Chemicals --- Medicine --- Pharmacology --- Poisoning --- Poisons --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Medical sciences --- Toxicology --- Composition --- Proteins . --- Nanoscience --- Physics --- Nano science --- Nanoscale science --- Nanosciences --- Science --- Biological physics --- Drug effects --- Medical pharmacology --- Chemotherapy --- Drugs --- Pharmacy --- Proteids --- Biomolecules --- Polypeptides --- Proteomics --- Physiological effect