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DHP Channel
Cav1.1 also known as the calcium channel, voltage-dependent, L type, alpha 1S subunit, (CACNA1S), is a protein which in humans is encoded by the ''CACNA1S'' gene. It is also known as CACNL1A3 and the dihydropyridine receptor (DHPR, so named due to the blocking action DHP has on it). Function This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. Cav1.1 is a voltage-dependent calcium channel found in the transverse tubule of muscles. In skeletal muscle it associates with the ryanodine receptor RyR1 of the sarcoplasmic reticulum via a mechanical linkage. It senses the voltage change caused by the end-plate potential from nervous stimulation and propagated by sodium channels as action potentials to the T-tubules. It was previously thought tha ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabolic reactions, DNA replication, Cell signaling, responding to stimuli, providing Cytoskeleton, structure to cells and Fibrous protein, organisms, and Intracellular transport, transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the Nucleic acid sequence, nucleotide sequence of their genes, and which usually results in protein folding into a specific Protein structure, 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called pep ...
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Membrane Potential
Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. It equals the interior potential minus the exterior potential. This is the energy (i.e. work) per charge which is required to move a (very small) positive charge at constant velocity across the cell membrane from the exterior to the interior. (If the charge is allowed to change velocity, the change of kinetic energy and production of radiation must be taken into account.) Typical values of membrane potential, normally given in units of milli volts and denoted as mV, range from −80 mV to −40 mV. For such typical negative membrane potentials, positive work is required to move a positive charge from the interior to the exterior. However, thermal kinetic energy allows ions to overcome the potential difference. For a selectively permeable membrane, this permits a net flow against the gradient. This is a kind ...
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Neuromuscular Junction
A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to function—and even just to maintain muscle tone, avoiding atrophy. In the neuromuscular system, nerves from the central nervous system and the peripheral nervous system are linked and work together with muscles. Synaptic transmission at the neuromuscular junction begins when an action potential reaches the presynaptic terminal of a motor neuron, which activates voltage-gated calcium channels to allow calcium ions to enter the neuron. Calcium ions bind to sensor proteins (synaptotagmins) on synaptic vesicles, triggering vesicle fusion with the cell membrane and subsequent neurotransmitter release from the motor neuron into the synaptic cleft. In vertebrates, motor neurons release acetylcholine (ACh), a small molecule neurotransmitter, which ...
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Calcium Channel
A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium channels are regulated by the binding of a ligand.Striggow F, Ehrlich BE (August 1996). "Ligand-gated calcium channels inside and out". ''Current Opinion in Cell Biology''. 8 (4): 490–495. Doi (identifier), doi:doi:10.1016/S0955-0674(96)80025-1, 10.1016/S0955-0674(96)80025-1. PMID (identifier), PMID]8791458 Other calcium channels can also be regulated by both voltage and ligands to provide precise control over ion flow. Some cation channels allow calcium as well as other cations to pass through the membrane. Calcium channels can participate in the creation of Action potential, action potentials across cell membranes. Calcium channels can also be used to release calcium ions as Second messenger system, second messengers within the cell, affec ...
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Channel Blocker
A channel blocker is the biological mechanism in which a particular molecule is used to prevent the opening of ion channels in order to produce a physiological response in a cell. Channel blocking is conducted by different types of molecules, such as cations, anions, amino acids, and other chemicals. These blockers act as ion channel antagonists, preventing the response that is normally provided by the opening of the channel. Ion channels permit the selective passage of ions through cell membranes by utilizing proteins that function as pores, which allow for the passage of electrical charge in and out of the cell. These ion channels are most often gated, meaning they require a specific stimulus to cause the channel to open and close. These ion channel types regulate the flow of charged ions across the membrane and therefore mediate membrane potential of the cell. Molecules that act as channel blockers are important in the field of pharmacology, as a large portion of drug design ...
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Malignant Hyperthermia
Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complications can include muscle breakdown and high blood potassium. Most people who are susceptible to MH are generally unaffected when not exposed to triggering agents. Exposure to triggering agents (certain volatile anesthetic agents or succinylcholine) can lead to the development of MH in those who are susceptible. Susceptibility can occur due to at least six genetic mutations, with the most common one being of the '' RYR1'' gene. These genetic variations are often inherited in an autosomal dominant manner. The condition may also occur as a new mutation or be associated with a number of inherited muscle diseases, such as central core disease. In susceptible individuals, the medications induce the release of stored calcium ions within ...
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Hyperkalemic Periodic Paralysis
Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis. Onset usually occurs in early childhood, but it still occurs with adults. The mutation causing this disorder is autosomal dominant on the SCN4A gene with linkage to the sodium channel expressed in muscle. The mutation causes single amino acid changes in parts of the channel which are important for inactivation. These mutations impair "ball and chain" fast inactivation of SCN4A following an action potential. Signs and symptoms Hyperkalemic periodic paralysis causes episodes of extreme muscle weakness, with attacks often beginning in childhood. Depending on the type and severity of the HyperKPP, it can increase or stabili ...
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Resting Potential
The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential. The resting membrane potential has a value of approximately −70 mV or −0.07 V. Apart from the latter two, which occur in excitable cells (neurons, muscles, and some secretory cells in glands), membrane voltage in the majority of non-excitable cells can also undergo changes in response to environmental or intracellular stimuli. The resting potential exists due to the differences in membrane permeabilities for potassium, sodium, calcium, and chloride ions, which in turn result from functional activity of various ion channels, ion transporters, and exchangers. Conventionally, resting membrane potential can be defined as a relatively stable, ground value of transmembrane voltage in animal and plant cells. Because the membrane pe ...
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Excitation-contraction Coupling
Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as when holding something heavy in the same position. The termination of muscle contraction is followed by muscle relaxation, which is a return of the muscle fibers to their low tension-generating state. For the contractions to happen, the muscle cells must rely on the change in action of two types of filaments: thin and thick filaments. The major constituent of thin filaments is a chain formed by helical coiling of two strands of actin, and thick filaments dominantly consist of chains of the motor-protein myosin. Together, these two filaments form myofibrils - the basic functional organelles in the skeletal muscle system. In vertebrates, skeletal muscle contractions are neurogenic as they require synaptic input from motor neurons. A ...
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Action Potential
An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of Membrane potential#Cell excitability, excitable cells, which include animal cells like neurons and myocyte, muscle cells, as well as some plant cells. Certain endocrine cells such as pancreatic beta cells, and certain cells of the anterior pituitary gland are also excitable cells. In neurons, action potentials play a central role in cell–cell interaction, cell–cell communication by providing for—or with regard to saltatory conduction, assisting—the propagation of signals along the neuron's axon toward axon terminal, synaptic boutons situated at the ends of an axon; these signals can then connect wit ...
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End-plate Potential
End plate potentials (EPPs) are the voltages which cause depolarization of skeletal muscle fibers caused by neurotransmitters binding to the postsynaptic membrane in the neuromuscular junction. They are called "end plates" because the postsynaptic terminals of muscle fibers have a large, saucer-like appearance. When an action potential reaches the axon terminal of a motor neuron, vesicles carrying neurotransmitters (mostly acetylcholine) are Exocytosis, exocytosed and the contents are released into the neuromuscular junction. These neurotransmitters bind to receptors on the postsynaptic membrane and lead to its depolarization. In the absence of an action potential, acetylcholine vesicles spontaneously leak into the neuromuscular junction and cause very small depolarizations in the postsynaptic membrane. This small response (~0.4mV) is called a miniature end plate potential (MEPP) and is generated by one acetylcholine-containing vesicle. It represents the smallest possible depol ...
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Sarcoplasmic Reticulum
The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other cells. The main function of the SR is to store calcium ions (Ca2+). Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels are controlled tightly, and can be released int ...
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