Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors respond to drugs, including the nicotinic receptor agonist nicotine, they are found in the central and peripheral nervous system and many other tissues of many organisms, including humans. At the neuromuscular junction they are the primary receptor in muscle for motor nerve-muscle communication that controls muscle contraction. In the peripheral nervous system: they transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system, they are the receptors found on skeletal muscle that receive acetylcholine released to signal for muscular contraction. In the immune system, nAChRs regulate inflammatory processes and signal through distinct intracellular pathways. In insects, the cholinergic system is limited to the central nervous system; the nicotinic receptors are considered cholinergic receptors.
Nicotinic receptors get their name from nicotine, which does not stimulate the muscarinic acetylcholine receptor, but instead selectively binds to the nicotinic receptor. The muscarinic acetylcholine receptor gets its name from a chemical that selectively attaches to that receptor — muscarine. Acetylcholine itself binds to both nicotinic acetylcholine receptors; as ionotropic receptors, nAChRs are directly linked to ion channels. New evidence suggests that these receptors can use second messengers in some cases. Nicotinic acetylcholine receptors are the best-studied of the ionotropic receptors. Since nicotinic receptors help transmit outgoing signals for the sympathetic and parasympathetic systems, nicotinic receptor antagonists such as hexamethonium interfere with the transmission of these signals. Thus, for example, nicotinic receptor antagonists interfere with the baroreflex that corrects changes in blood pressure by sympathetic and parasympathetic stimulation of the heart. Nicotinic receptors, with a molecular mass of 290 kDa, are made up of five subunits, arranged symmetrically around a central pore.
Each subunit comprises four transmembrane domains with both the N- and C-terminus located extracellularly. They possess similarities with GABAA receptors, glycine receptors, the type 3 serotonin receptors, or the signature Cys-loop proteins. In vertebrates, nicotinic receptors are broadly classified into two subtypes based on their primary sites of expression: muscle-type nicotinic receptors and neuronal-type nicotinic receptors. In the muscle-type receptors, found at the neuromuscular junction, receptors are either the embryonic form, composed of α1, β1, γ, δ subunits in a 2:1:1:1 ratio, or the adult form composed of α1, β1, δ, ε subunits in a 2:1:1:1 ratio; the neuronal subtypes are various homomeric or heteromeric combinations of twelve different nicotinic receptor subunits: α2−α10 and β2−β4. Examples of the neuronal subtypes include: 32, 23, 23, α4α6β32, 5, many others. In both muscle-type and neuronal-type receptors, the subunits are similar to one another in the hydrophobic regions. A number of electron microscopy and x-ray crystallography studies have provided high resolution structural information for muscle and neuronal nAChRs and their binding domains.
As with all ligand-gated ion channels, opening of the nAChR channel pore requires the binding of a chemical messenger. Several different terms are used to refer to the molecules that bind receptors, such as ligand, agonist, or transmitter; as well as the endogenous agonist acetylcholine, agonists of the nAChR include nicotine and choline. Nicotinic antagonists that block the receptor include mecamylamine, dihydro-β-erythroidine, hexamethonium. In muscle-type nAChRs, the acetylcholine binding sites are located at the α and either ε or δ subunits interface. In neuronal nAChRs, the binding site is located at the interface of an α and a β subunit or between two α subunits in the case of α7 receptors; the binding site is located in the extracellular domain near the N terminus. When an agonist binds to the site, all present subunits undergo a conformational change and the channel is opened and a pore with a diameter of about 0.65 nm opens. Nicotinic AChRs may exist in different interconvertible conformational states.
Binding of an agonist stabilises the desensitised states. In normal physiological conditions, the receptor needs two molecules of ACh to open. Opening of the channel allows positively charged ions to move across it; the net flow of positively charged ions is inward. The nAChR is a non-selective cation channel, meaning that several different positively charged ions can cross through, it is permeable to Na+ and K+, with some subunit combinations that are permeable to Ca2+. The amount of sodium and potassium the channels allow through their pores varies from 50–110 pS, with the conductance depending on the specific subunit composition as well as the permeant ion. Many neuronal nAChRs can affect the release of other neurotransmitters; the channel opens and tends to remain open until the agonist diffuses away, which takes about 1 millisecond. However, AChRs can spontaneously open with no ligands bound or can spontaneously close with ligands bound, mutations in the channel can shift the likelihood of either event.
Therefore, ACh binding changes the probability of pore opening. The nAChR is unable to bind ACh. The
An axon, or nerve fiber, is a long, slender projection of a nerve cell, or neuron, in vertebrates, that conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body, from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction has caused many inherited and acquired neurological disorders which can affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, group C nerve fibers. Groups A and B are myelinated, group C are unmyelinated; these groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, Type IV. An axon is one of two types of cytoplasmic protrusions from the cell body of a neuron.
Axons are distinguished from dendrites by several features, including shape and function. Some types of neurons have no transmit signals from their dendrites. In some species, axons can emanate from dendrites and these are known as axon-carrying dendrites. No neuron has more than one axon. Axons are covered by a membrane known as an axolemma. Most axons branch, in some cases profusely; the end branches of an axon are called telodendria. The swollen end of a telodendron is known as the axon terminal which joins the dendron or cell body of another neuron forming a synaptic connection. Axons make contact with other cells—usually other neurons but sometimes muscle or gland cells—at junctions called synapses. In some circumstances, the axon of one neuron may form a synapse with the dendrites of the same neuron, resulting in an autapse. At a synapse, the membrane of the axon adjoins the membrane of the target cell, special molecular structures serve to transmit electrical or electrochemical signals across the gap.
Some synaptic junctions appear along the length of an axon as it extends—these are called en passant synapses and can be in the hundreds or the thousands along one axon. Other synapses appear as terminals at the ends of axonal branches. A single axon, with all its branches taken together, can innervate multiple parts of the brain and generate thousands of synaptic terminals. A bundle of axons make a nerve tract in the central nervous system, a fascicle in the peripheral nervous system. In placental mammals the largest white matter tract in the brain is the corpus callosum, formed of some 20 million axons in the human brain. Axons are the primary transmission lines of the nervous system, as bundles they form nerves; some axons can extend up to more while others extend as little as one millimeter. The longest axons in the human body are those of the sciatic nerve, which run from the base of the spinal cord to the big toe of each foot; the diameter of axons is variable. Most individual axons are microscopic in diameter.
The largest mammalian axons can reach a diameter of up to 20 µm. The squid giant axon, specialized to conduct signals rapidly, is close to 1 millimetre in diameter, the size of a small pencil lead; the numbers of axonal telodendria can differ from one nerve fiber to the next. Axons in the central nervous system show multiple telodendria, with many synaptic end points. In comparison, the cerebellar granule cell axon is characterized by a single T-shaped branch node from which two parallel fibers extend. Elaborate branching allows for the simultaneous transmission of messages to a large number of target neurons within a single region of the brain. There are two types of axons in the nervous system: unmyelinated axons. Myelin is a layer of a fatty insulating substance, formed by two types of glial cells Schwann cells and oligodendrocytes. In the peripheral nervous system Schwann cells form the myelin sheath of a myelinated axon. In the central nervous system oligodendrocytes form the insulating myelin.
Along myelinated nerve fibers, gaps in the myelin sheath known as nodes of Ranvier occur at evenly spaced intervals. The myelination enables an rapid mode of electrical impulse propagation called saltatory conduction; the myelinated axons from the cortical neurons form the bulk of the neural tissue called white matter in the brain. The myelin gives the white appearance to the tissue in contrast to the grey matter of the cerebral cortex which contains the neuronal cell bodies. A similar arrangement is seen in the cerebellum. Bundles of myelinated axons make up the nerve tracts in the CNS. Where these tracts cross the midline of the brain to connect opposite regions they are called commissures; the largest of these is the corpus callosum that connects the two cerebral hemispheres, this has around 20 million axons. The structure of a neuron is seen to consist of two separate functional regions, or compartments – the cell body together with the dendrites as one region, the axonal region as the other.
The axonal region or compart
The extraocular muscles are the six muscles that control movement of the eye and one muscle that controls eyelid elevation. The actions of the six muscles responsible for eye movement depend on the position of the eye at the time of muscle contraction. Since only a small part of the eye called the fovea provides sharp vision, the eye must move to follow a target. Eye movements must be fast; this is seen in scenarios like reading. Although under voluntary control, most eye movement is accomplished without conscious effort. How the integration between voluntary and involuntary control of the eye occurs is a subject of continuing research, it is known, that the vestibulo-ocular reflex plays an important role in the involuntary movement of the eye. Four of the extraocular muscles have their origin in the back of the orbit in a fibrous ring called the annulus of Zinn: the four rectus muscles; the four rectus muscles attach directly to the front half of the eye, are named after their straight paths. Note that medial and lateral are relative terms.
Medial indicates near the midline, lateral describes a position away from the midline. Thus, the medial rectus is the muscle closest to the nose; the superior and inferior recti do not pull straight back on the eye, because both muscles pull medially. This posterior medial angle causes the eye to roll with contraction of either the superior rectus or inferior rectus muscles; the extent of rolling in the recti is less than the oblique, opposite from it. The superior oblique muscle originates at the back of the orbit, getting rounder as it courses forward to a rigid, cartilaginous pulley, called the trochlea, on the upper, nasal wall of the orbit; the muscle becomes tendinous about 10mm before it passes through the pulley, turning across the orbit, inserts on the lateral, posterior part of the globe. Thus, the superior oblique travels posteriorly for the last part of its path, going over the top of the eye. Due to its unique path, the superior oblique, when activated, pulls the eye laterally; the last muscle is the inferior oblique, which originates at the lower front of the nasal orbital wall, passes under the LR to insert on the lateral, posterior part of the globe.
Thus, the inferior oblique pulls the eye laterally. The movements of the extraocular muscles take place under the influence of a system of extraocular muscle pulleys, soft tissue pulleys in the orbit; the extraocular muscle pulley system is fundamental to the movement of the eye muscles, in particular to ensure conformity to Listing's law. Certain diseases of the pulleys cause particular patterns of incomitant strabismus. Defective pulley functions can be improved by surgical interventions; the extraocular muscles are supplied by branches of the ophthalmic artery. This is done either directly or indirectly, as in the lateral rectus muscle, via the lacrimal artery, a main branch of the ophthalmic artery. Additional branches of the ophthalmic artery include the ciliary arteries, which branch into the anterior ciliary arteries; each rectus muscle receives blood from two anterior ciliary arteries, except for the lateral rectus muscle, which receives blood from only one. The exact number and arrangement of these cilary arteries may vary.
Branches of the infraorbital artery supply inferior oblique muscles. The nuclei or bodies of these nerves are found in the brain stem; the nuclei of the abducens and oculomotor nerves are connected. This is important in coordinating the motion of the lateral rectus in one eye and the medial action on the other. In one eye, in two antagonistic muscles, like the lateral and medial recti, contraction of one leads to inhibition of the other. Muscles show small degrees of activity when resting, keeping the muscles taut; this "tonic" activity is brought on by discharges of the motor nerve to the muscle. The extraocular muscles develop along with the fatty tissue of the eye socket. There are three centers of growth that are important in the development of the eye, each is associated with a nerve. Hence the subsequent nerve supply of the eye muscles is from three cranial nerves; the development of the extraocular muscles is dependent on the normal development of the eye socket, while the formation of the ligament is independent.
Below is a table of each of the extraocular muscles and their innervation and insertions, the primary actions of the muscles. Intermediate directions are controlled by simultaneous actions of multiple muscles; when one shifts the gaze horizontally, one eye will move laterally and the other will move medially. This may be neurally coordinated by the central nervous system, to make the eyes move together and involuntarily; this is a key factor in the study of strabismus, the inability of the eyes to be directed to one point. There are two main kinds of movement: disjunctive; the former is typical when shifting gaze right or left, the latter is convergence of the two eyes on a near object. Disjunction can be performed voluntarily, but is triggered by the nearness of the target object. A "see-saw" movement, one eye looking up and the other down, is possible, but not voluntarily. To avoi
The mitochondrion is a double-membrane-bound organelle found in most eukaryotic organisms. Some cells in some multicellular organisms may, lack them. A number of unicellular organisms, such as microsporidia and diplomonads, have reduced or transformed their mitochondria into other structures. To date, only one eukaryote, Monocercomonoides, is known to have lost its mitochondria; the word mitochondrion comes from the Greek μίτος, mitos, "thread", χονδρίον, chondrion, "granule" or "grain-like". Mitochondria generate most of the cell's supply of adenosine triphosphate, used as a source of chemical energy. A mitochondrion was thus termed the powerhouse of the cell. Mitochondria are between 0.75 and 3 μm in diameter but vary in size and structure. Unless stained, they are not visible. In addition to supplying cellular energy, mitochondria are involved in other tasks, such as signaling, cellular differentiation, cell death, as well as maintaining control of the cell cycle and cell growth. Mitochondrial biogenesis is in turn temporally coordinated with these cellular processes.
Mitochondria have been implicated in several human diseases, including mitochondrial disorders, cardiac dysfunction, heart failure and autism. The number of mitochondria in a cell can vary by organism and cell type. For instance, red blood cells have no mitochondria, whereas liver cells can have more than 2000; the organelle is composed of compartments. These compartments or regions include the outer membrane, the intermembrane space, the inner membrane, the cristae and matrix. Although most of a cell's DNA is contained in the cell nucleus, the mitochondrion has its own independent genome that shows substantial similarity to bacterial genomes. Mitochondrial proteins vary depending on the species. In humans, 615 distinct types of protein have been identified from cardiac mitochondria, whereas in rats, 940 proteins have been reported; the mitochondrial proteome is thought to be dynamically regulated. The first observations of intracellular structures that represented mitochondria were published in the 1840s.
Richard Altmann, in 1890, established them as cell organelles and called them "bioblasts". The term "mitochondria" was coined by Carl Benda in 1898. Leonor Michaelis discovered that Janus green can be used as a supravital stain for mitochondria in 1900. In 1904, Friedrich Meves, made the first recorded observation of mitochondria in plants in cells of the white waterlily, Nymphaea alba and in 1908, along with Claudius Regaud, suggested that they contain proteins and lipids. Benjamin F. Kingsbury, in 1912, first related them with cell respiration, but exclusively based on morphological observations. In 1913, particles from extracts of guinea-pig liver were linked to respiration by Otto Heinrich Warburg, which he called "grana". Warburg and Heinrich Otto Wieland, who had postulated a similar particle mechanism, disagreed on the chemical nature of the respiration, it was not until 1925, when David Keilin discovered cytochromes, that the respiratory chain was described. In 1939, experiments using minced muscle cells demonstrated that cellular respiration using one oxygen atom can form two adenosine triphosphate molecules, and, in 1941, the concept of the phosphate bonds of ATP being a form of energy in cellular metabolism was developed by Fritz Albert Lipmann.
In the following years, the mechanism behind cellular respiration was further elaborated, although its link to the mitochondria was not known. The introduction of tissue fractionation by Albert Claude allowed mitochondria to be isolated from other cell fractions and biochemical analysis to be conducted on them alone. In 1946, he concluded that cytochrome oxidase and other enzymes responsible for the respiratory chain were isolated to the mitochondria. Eugene Kennedy and Albert Lehninger discovered in 1948 that mitochondria are the site of oxidative phosphorylation in eukaryotes. Over time, the fractionation method was further developed, improving the quality of the mitochondria isolated, other elements of cell respiration were determined to occur in the mitochondria; the first high-resolution electron micrographs appeared in 1952, replacing the Janus Green stains as the preferred way of visualising the mitochondria. This led to a more detailed analysis of the structure of the mitochondria, including confirmation that they were surrounded by a membrane.
It showed a second membrane inside the mitochondria that folded up in ridges dividing up the inner chamber and that the size and shape of the mitochondria varied from cell to cell. The popular term "powerhouse of the cell" was coined by Philip Siekevitz in 1957. In 1967, it was discovered. In 1968, methods were developed for mapping the mitochondrial genes, with the genetic and physical map of yeast mitochondrial DNA being completed in 1976. There are two hypotheses about the origin of mitochondria: autogenous; the endosymbiotic hypothesis suggests that mitochondria were prokaryotic cells, capable of implementing oxidative mechanisms that were not possible for eukaryotic cells. In the autogenous hypothesis, mitochondria were born by splitting off a portion of DNA from the nucleus of the eukaryotic cell at the time of divergence with the prokaryotes. Since mitochondria have many features in common with bacteria, the endosymbiotic hypothesis is more accepted. A mitochondrion contains DNA, which i
Blurred vision is an ocular symptom. There are many causes of blurred vision: Use of atropine or other anticholinergics Presbyopia—Difficulty focusing on objects that are close. Common in the elderly. Cataracts—Cloudiness over the eye's lens, causing poor night-time vision, halos around lights, and sensitivity to glare. Daytime vision is affected. Common in the elderly. Glaucoma—Increased pressure in the eye, causing poor night vision, blind spots, loss of vision to either side. A major cause of blindness. Glaucoma can happen or suddenly—if sudden, it is a medical emergency. Diabetes—Poorly controlled blood sugar can lead to temporary swelling of the lens of the eye, resulting in blurred vision. While it resolves if blood sugar control is reestablished, it is believed repeated occurrences promote the formation of cataracts. Diabetic retinopathy—This complication of diabetes can lead to bleeding into the retina. Another common cause of blindness. Hypervitaminosis A—Excess consumption of vitamin A can cause blurred vision.
Macular degeneration—Loss of central vision, blurred vision, distorted vision, colors appearing faded. The most common cause of blindness in people over age 60. Eye infection, inflammation, or injury. Sjögren's syndrome, a chronic autoimmune inflammatory disease that destroys moisture producing glands, including lacrimal Floaters—Tiny particles drifting across the eye. Although brief and harmless, they may be a sign of retinal detachment. Retinal detachment—Symptoms include floaters, flashes of light across your visual field, or a sensation of a shade or curtain hanging on one side of your visual field. Optic neuritis—Inflammation of the optic nerve from infection or multiple sclerosis. You may touch it through the eyelid. Stroke or transient ischemic attack Brain tumor Toxocara—A parasitic roundworm that can cause blurred vision Bleeding into the eye Temporal arteritis—Inflammation of an artery in the brain that supplies blood to the optic nerve. Migraine headaches—Spots of light, halos, or zigzag patterns are common symptoms prior to the start of the headache.
A retinal migraine is. Myopia—Blurred vision may be a systemic sign of local anaesthetic toxicity Reduced blinking—Lid closure that occurs too infrequently leads to irregularities of the tear film due to prolonged evaporation, thus resulting in disruptions in visual perception. Carbon monoxide poisoning—Reduced oxygen delivery can effect many areas of the body including vision. Other symptoms caused by CO include vertigo and sensitivity to light
Pupillary light reflex
The pupillary light reflex or photopupillary reflex is a reflex that controls the diameter of the pupil, in response to the intensity of light that falls on the retinal ganglion cells of the retina in the back of the eye, thereby assisting in adaptation to various levels of lightness/darkness. A greater intensity of light causes the pupil to constrict, whereas a lower intensity of light causes the pupil to dilate. Thus, the pupillary light reflex regulates the intensity of light entering the eye. Light shone into one eye will cause both pupils to constrict. Pupil is where light enters the eye. Based on analogy with a camera, pupil is equivalent to aperture, whereas iris is equivalent to the diaphragm. Pupillary reflex should have been named iris reflex, because iris is the actual muscular structure that responds to light and pupil is the passive opening formed by the active iris. Pupillary reflex is synonymous with pupillary response, which may be pupillary constriction or dilation. Pupillary reflex is conceptually linked to the side of the reacting pupil, not to the side from which light stimulation originates.
Left pupillary reflex refers to the response of the left pupil to light, regardless of which eye is exposed to a light source. Right pupillary reflex means reaction of the right pupil, whether light is shone into the left eye, right eye, or both eyes. In contrast, the terms direct and consensual refers to the side where the light source comes from, relative to the side of the reacting pupil. A direct pupillary reflex is pupillary response to light. A consensual pupillary reflex is response of a pupil to light, thus there are four types of pupillary light reflexes, based on this terminology of absolute and relative laterality: Left direct pupillary reflex is the left pupil's response to light entering the left eye, the ipsilateral eye. Left consensual pupillary reflex is the left pupil's indirect response to light entering the right eye, the contralateral eye. Right direct pupillary reflex is the right pupil's response to light entering the right eye, the ipsilateral eye. Right consensual pupillary reflex is the right pupil's indirect response to light entering the left eye, the contralateral eye.
The pupillary light reflex neural pathway on each side has two efferent limbs. The afferent limb has nerve fibers running within the optic nerve; each efferent limb has nerve fibers running along the oculomotor nerve. The afferent limb carries sensory input. Anatomically, the afferent limb consists of the retina, the optic nerve, the pretectal nucleus in the midbrain, at level of superior colliculus. Ganglion cells of the retina project fibers through the optic nerve to the ipsilateral pretectal nucleus; the efferent limb is the pupillary motor output from the pretectal nucleus to the ciliary sphincter muscle of the iris. The pretectal nucleus projects crossed and uncrossed fibers to the ipsilateral and contralateral Edinger-Westphal nuclei, which are located in the midbrain; each Edinger-Westphal nucleus gives rise to preganglionic parasympathetic fibers which exit with CN III and synapse with postganglionic parasympathetic neurons in the ciliary ganglion. Postganglionic nerve fibers leave the ciliary ganglion to innervate the ciliary sphincter.
Each afferent limb has one ipsilateral and one contralateral. The ipsilateral efferent limb transmits nerve signals for direct light reflex of the ipsilateral pupil; the contralateral efferent limb causes consensual light reflex of the contralateral pupil. The optic nerve, or more the photosensitive ganglion cells through the retinohypothalamic tract, is responsible for the afferent limb of the pupillary reflex; the oculomotor nerve is responsible for the efferent limb of the pupillary reflex. Retina: The pupillary reflex pathway begins with the photosensitive retinal ganglion cells, which convey information via the optic nerve, the most peripheral, portion of, the optic disc; some axons of the optic nerve connect to the pretectal nucleus of the upper midbrain instead of the cells of the lateral geniculate nucleus. These intrinsic photosensitive ganglion cells are referred to as melanopsin-containing cells, they influence circadian rhythms as well as the pupillary light reflex. Pretectal nuclei: From the neuronal cell bodies in some of the pretectal nuclei, axons synapse on neurons in the Edinger-Westphal nucleus.
Those neurons are the preganglionic cells with axons that run in the oculomotor nerves to the ciliary ganglia. Edinger-Westphal nuclei: Parasympathetic neuronal axons in the oculomotor nerve synapse on ciliary ganglion neurons. Ciliary ganglia: Short post-ganglionic ciliary nerves leave the ciliary ganglion to innervate the Iris sphincter muscle of the iris; the pupillary response to light is not purely reflexive, but is modulated by cognitive factors, such as attention and the way visual input is interpreted. For example, if a bright stimulus is presented to one eye, a dark stimulus to the other eye, perception alternates between the two eyes: Sometimes the dark stimulus is perceived, sometimes the bright stimulus, but never both at the same time. Using this technique, it has been shown the pupil is smaller when a bright stimulus dominates awareness, relative to when a dark stimulus dominates awareness; this shows t