Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Secretory Vesicles: Vesicles derived from the GOLGI APPARATUS containing material to be released at the cell surface.Chromaffin Cells: Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia (PARAGANGLIA, CHROMAFFIN) of the sympathetic nervous system.Cytoplasmic Granules: Condensed areas of cellular material that may be bounded by a membrane.Synaptotagmins: A family of vesicular transport proteins characterized by an N-terminal transmembrane region and two C-terminal calcium-binding domains.SNARE Proteins: A superfamily of small proteins which are involved in the MEMBRANE FUSION events, intracellular protein trafficking and secretory processes. They share a homologous SNARE motif. The SNARE proteins are divided into subfamilies: QA-SNARES; QB-SNARES; QC-SNARES; and R-SNARES. The formation of a SNARE complex (composed of one each of the four different types SNARE domains (Qa, Qb, Qc, and R)) mediates MEMBRANE FUSION. Following membrane fusion SNARE complexes are dissociated by the NSFs (N-ETHYLMALEIMIDE-SENSITIVE FACTORS), in conjunction with SOLUBLE NSF ATTACHMENT PROTEIN, i.e., SNAPs (no relation to SNAP 25.)Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electric Capacitance: The ability of a substrate to retain an electrical charge.Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.Vesicular Transport Proteins: A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.Synaptosomal-Associated Protein 25: A ubiquitous target SNARE protein that interacts with SYNTAXIN and SYNAPTOBREVIN. It is a core component of the machinery for intracellular MEMBRANE FUSION. The sequence contains 2 SNARE domains, one is the prototype for the Qb-SNARES, and the other is the prototype for the Qc-SNARES.Weibel-Palade Bodies: Rod-shaped storage granules for VON WILLEBRAND FACTOR specific to endothelial cells.rab3A GTP-Binding Protein: The most abundant member of the RAB3 GTP-BINDING PROTEINS. It is involved in calcium-dependent EXOCYTOSIS and is localized to neurons and neuroendocrine cells. This enzyme was formerly listed as EC 3.6.1.47.Qa-SNARE Proteins: A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES.R-SNARE Proteins: SNARE proteins where the central amino acid residue of the SNARE motif is an ARGININE. They are classified separately from the Q-SNARE PROTEINS where the central amino acid residue of the SNARE motif is a GLUTAMINE. This subfamily contains the vesicle associated membrane proteins (VAMPs) based on similarity to the prototype for the R-SNAREs, VAMP2 (synaptobrevin 2).Membrane Fusion: The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.Syntaxin 1: A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.Acrosome: The cap-like structure covering the anterior portion of SPERM HEAD. Acrosome, derived from LYSOSOMES, is a membrane-bound organelle that contains the required hydrolytic and proteolytic enzymes necessary for sperm penetration of the egg in FERTILIZATION.rab3 GTP-Binding Proteins: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in calcium-dependent EXOCYTOSIS. This enzyme was formerly listed as EC 3.6.1.47.Synaptotagmin I: A vesicular transport protein expressed predominately in NEURONS. Synaptotagmin helps regulate EXOCYTOSIS of SYNAPTIC VESICLES and appears to serve as a calcium sensor to trigger NEUROTRANSMITTER release. It also acts as a nerve cell receptor for certain BOTULINUM TOXINS.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Munc18 Proteins: A family of proteins involved in intracellular membrane trafficking. They interact with SYNTAXINS and play important roles in vesicular docking and fusion during EXOCYTOSIS. Their name derives from the fact that they are related to Unc-18 protein, C elegans.Pyridinium CompoundsVesicle-Associated Membrane Protein 2: A synaptic membrane protein involved in MEMBRANE FUSION of SYNAPTIC VESICLES with the presynaptic membranes. It is the prototype member of the R-SNARE PROTEINS.Nerve Tissue ProteinsEndocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.rab GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.Tetanus Toxin: Protein synthesized by CLOSTRIDIUM TETANI as a single chain of ~150 kDa with 35% sequence identity to BOTULINUM TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal CONVULSIONS.Acrosome Reaction: Changes that occur to liberate the enzymes of the ACROSOME of a sperm (SPERMATOZOA). Acrosome reaction allows the sperm to penetrate the ZONA PELLUCIDA and enter the OVUM during FERTILIZATION.Adrenal Medulla: The inner portion of the adrenal gland. Derived from ECTODERM, adrenal medulla consists mainly of CHROMAFFIN CELLS that produces and stores a number of NEUROTRANSMITTERS, mainly adrenaline (EPINEPHRINE) and NOREPINEPHRINE. The activity of the adrenal medulla is regulated by the SYMPATHETIC NERVOUS SYSTEM.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Chromaffin Granules: Organelles in CHROMAFFIN CELLS located in the adrenal glands and various other organs. These granules are the site of the synthesis, storage, metabolism, and secretion of EPINEPHRINE and NOREPINEPHRINE.Spider Venoms: Venoms of arthropods of the order Araneida of the ARACHNIDA. The venoms usually contain several protein fractions, including ENZYMES, hemolytic, neurolytic, and other TOXINS, BIOLOGICAL.Transport Vesicles: Vesicles that are involved in shuttling cargo from the interior of the cell to the cell surface, from the cell surface to the interior, across the cell or around the cell to various locations.Islets of Langerhans: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.N-Ethylmaleimide-Sensitive Proteins: ATPases that are members of the AAA protein superfamily (ATPase family Associated with various cellular Activities). The NSFs functions, acting in conjunction with SOLUBLE NSF ATTACHMENT PROTEINS (i.e. SNAPs, which have no relation to SNAP 25), are to dissociate SNARE complexes.Qc-SNARE Proteins: A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the C-terminal SNARE domain of SNAP-25 and which also are most similar to the C-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.Qb-SNARE Proteins: A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the N-terminal SNARE domain of SNAP-25 and which also are most similar to the N-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.Botulinum Toxins: Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS.Synaptotagmin II: A vesicular transport protein that was originally characterized as an inositol polyphosphate binding protein. Synaptotagmin II helps regulate EXOCYTOSIS of SYNAPTIC VESICLES and appears to serve as a calcium sensor to trigger NEUROTRANSMITTER release. It also acts as a nerve cell receptor for certain BOTULINUM TOXINS.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Paramecium: A genus of ciliate protozoa that is often large enough to be seen by the naked eye. Paramecia are commonly used in genetic, cytological, and other research.Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.Neurotransmitter Agents: Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.Quaternary Ammonium Compounds: Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.Goldfish: Common name for Carassius auratus, a type of carp (CARPS).Ionophores: Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes.Cytoplasmic Vesicles: Membrane-limited structures derived from the plasma membrane or various intracellular membranes which function in storage, transport or metabolism.Vesicle-Associated Membrane Protein 3: A member of the vesicle associated membrane protein family. It has a broad tissue distribution and is involved in MEMBRANE FUSION events of the endocytic pathways.Cell Membrane Permeability: A quality of cell membranes which permits the passage of solvents and solutes into and out of cells.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins: SNARE binding proteins that facilitate the ATP hydrolysis-driven dissociation of the SNARE complex. They are required for the binding of N-ETHYLMALEIMIDE-SENSITIVE PROTEIN (NSF) to the SNARE complex which also stimulates the ATPASE activity of NSF. They are unrelated structurally to SNAP-25 PROTEIN.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Kinetics: The rate dynamics in chemical or physical systems.Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Streptolysins: Exotoxins produced by certain strains of streptococci, particularly those of group A (STREPTOCOCCUS PYOGENES), that cause HEMOLYSIS.Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.Mast Cells: Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Ovum: A mature haploid female germ cell extruded from the OVARY at OVULATION.Lysosomes: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Spermatozoa: Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility.Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Membrane Potentials: The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Fluorescent Dyes: Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.Paramecium tetraurelia: A species of ciliate protozoa. It is used in biomedical research.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Neuroendocrine Cells: Specialized NEURONS that produce hormones, such as NEUROPEPTIDES or BIOGENIC AMINES. They generally are in the NERVOUS SYSTEM, such as HYPOTHALAMUS, but can be found in other organs or systems. These neurons contain dense neurosecretory granules and PROPROTEIN CONVERTASES allowing the rapidly release of NEUROHORMONES into the blood circulation upon stimulation.Insulin-Secreting Cells: A type of pancreatic cell representing about 50-80% of the islet cells. Beta cells secrete INSULIN.Synaptic Membranes: Cell membranes associated with synapses. Both presynaptic and postsynaptic membranes are included along with their integral or tightly associated specializations for the release or reception of transmitters.Sea Urchins: Somewhat flattened, globular echinoderms, having thin, brittle shells of calcareous plates. They are useful models for studying FERTILIZATION and EMBRYO DEVELOPMENT.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Ionomycin: A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Fertilization: The fusion of a spermatozoon (SPERMATOZOA) with an OVUM thus resulting in the formation of a ZYGOTE.Dynamins: A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC 3.6.1.50.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Zona Pellucida: A tough transparent membrane surrounding the OVUM. It is penetrated by the sperm during FERTILIZATION.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.