In neuroscience, the threshold potential is the critical level to which a membrane potential must be depolarized to initiate an action potential. Threshold potentials are necessary to regulate and propagate signaling in both the central nervous system and the peripheral nervous system. Most the threshold potential is a membrane potential value between –50 and –55 mV, but can vary based upon several factors. A neuron's resting membrane potential can be altered to either increase or decrease likelihood of reaching threshold via sodium and potassium ions. An influx of sodium into the cell through open, voltage-gated sodium channels can depolarize the membrane past threshold and thus excite it while an efflux of potassium or influx of chloride can hyperpolarize the cell and thus inhibit threshold from being reached. Initial experiments revolved around the concept that any electrical change, brought about in neurons must occur through the action of ions; the German physical chemist Walther Nernst applied this concept in experiments to discover nervous excitability, concluded that the local excitatory process through a semi-permeable membrane depends upon the ionic concentration.
Ion concentration was shown to be the limiting factor in excitation. If the proper concentration of ions was attained, excitation would occur; this was the basis for discovering the threshold value. Along with reconstructing the action potential in the 1950s, Alan Lloyd Hodgkin and Andrew Huxley were able to experimentally determine the mechanism behind the threshold for excitation, it is known as the Hodgkin–Huxley model. Through use of voltage clamp techniques on a squid giant axon, they discovered that excitable tissues exhibit the phenomenon that a certain membrane potential must be reached in order to fire an action potential. Since the experiment yielded results through the observation of ionic conductance changes and Huxley used these terms to discuss the threshold potential, they suggested that there must be a discontinuity in the conductance of either sodium or potassium, but in reality both conductances tended to vary smoothly along with the membrane potential. They soon discovered that at threshold potential, the inward and outward currents, of sodium and potassium ions were equal and opposite.
As opposed to the resting membrane potential, the threshold potential's conditions exhibited a balance of currents that were unstable. Instability refers to the fact that any further depolarization activates more voltage-gated sodium channels, the incoming sodium depolarizing current overcomes the delayed outward current of potassium. At resting level, on the other hand, the potassium and sodium currents are equal and opposite in a stable manner, where a sudden, continuous flow of ions should not result; the basis is that at a certain level of depolarization, when the currents are equal and opposite in an unstable manner, any further entry of positive charge generates an action potential. This specific value of depolarization is otherwise known as the threshold potential; the threshold value controls whether or not the incoming stimuli are sufficient to generate an action potential. It relies on a balance of incoming excitatory stimuli; the potentials generated by the stimuli are additive, they may reach threshold depending on their frequency and amplitude.
Normal functioning of the central nervous system entails a summation of synaptic inputs made onto a neuron's dendritic tree. These local graded potentials, which are associated with external stimuli, reach the axon initial segment and build until they manage to reach the threshold value; the larger the stimulus, the greater the depolarization, or attempt to reach threshold. The task of depolarization requires several key steps; the ion conductances involved depend on the membrane potential and the time after the membrane potential changes. The phospholipid bilayer of the cell membrane is, in itself impermeable to ions; the complete structure of the cell membrane includes many proteins that are embedded in or cross the lipid bilayer. Some of those proteins allow for the specific passage of ions, ion channels. Leak potassium channels allow potassium to flow through the membrane in response to the disparity in concentrations of potassium inside and outside the cell; the loss of positive charges of the potassium ions from the inside of the cell results in a negative potential there compared to the extracellular surface of the membrane.
A much smaller "leak" of sodium into the cell results in the actual resting potential, about –70 mV, being less negative than the calculated potential for K+ alone, the equilibrium potential, about –90 mV. The sodium-potassium ATPase is an active transporter within the membrane that pumps potassium back into the cell and sodium out of the cell, maintaining the concentrations of both ions as well as preserving the voltage polarization. However, once a stimulus activates the voltage-gated sodium channels to open, positive sodium ions flood into the cell and the voltage increases; this process can be initiated by ligand or neurotransmitter binding to a ligand-gated channel. More sodium is outside the cell relative to the inside, the positive charge within the cell propels the outflow of potassium ions through delayed-rectifier voltage-gated potassium channels. Since the potassium channels within the cell membrane are delayed, any further entrance of sodium activates more and more voltage-gated sodium channels.
Depolarization above threshold results in an increase in the conductance of Na sufficient for inward sodium movement to swamp outwar
Physiology is the scientific study of the functions and mechanisms which work within a living system. As a sub-discipline of biology, the focus of physiology is on how organisms, organ systems, organs and biomolecules carry out the chemical and physical functions that exist in a living system. Central to an understanding of physiological functioning is the investigation of the fundamental biophysical and biochemical phenomena, the coordinated homeostatic control mechanisms, the continuous communication between cells; the physiologic state is the condition occurring from normal body function, while the pathological state is centered on the abnormalities that occur in animal diseases, including humans. According to the type of investigated organisms, the field can be divided into, animal physiology, plant physiology, cellular physiology and microbial physiology; the Nobel Prize in Physiology or Medicine is awarded to those who make significant achievements in this discipline by the Royal Swedish Academy of Sciences.
Human physiology seeks to understand the mechanisms that work to keep the human body alive and functioning, through scientific enquiry into the nature of mechanical and biochemical functions of humans, their organs, the cells of which they are composed. The principal level of focus of physiology is at the level of systems within systems; the endocrine and nervous systems play major roles in the reception and transmission of signals that integrate function in animals. Homeostasis is a major aspect with regard to such interactions within plants as well as animals; the biological basis of the study of physiology, integration refers to the overlap of many functions of the systems of the human body, as well as its accompanied form. It is achieved through communication that occurs in a variety of both electrical and chemical. Changes in physiology can impact the mental functions of individuals. Examples of this would be toxic levels of substances. Change in behavior as a result of these substances is used to assess the health of individuals.
Much of the foundation of knowledge in human physiology was provided by animal experimentation. Due to the frequent connection between form and function and anatomy are intrinsically linked and are studied in tandem as part of a medical curriculum. Plant physiology is a subdiscipline of botany concerned with the functioning of plants. Related fields include plant morphology, plant ecology, cell biology, genetics and molecular biology. Fundamental processes of plant physiology include photosynthesis, plant nutrition, nastic movements, photomorphogenesis, circadian rhythms, seed germination and stomata function and transpiration. Absorption of water by roots, production of food in the leaves, growth of shoots towards light are examples of plant physiology. Although there are differences between animal and microbial cells, the basic physiological functions of cells can be divided into the processes of cell division, cell signaling, cell growth, cell metabolism. Microorganisms can be found everywhere on Earth.
Types of microorganisms include archaea, eukaryotes, protists and micro-plants. Microbes are important in human culture and health in many ways, serving to ferment foods, treat sewage, produce fuel and other bioactive compounds, they are essential tools in biology as model organisms and have been put to use in biological warfare and bioterrorism. They are a vital component of fertile soils. In the human body microorganisms make up the human microbiota including the essential gut flora, they are the pathogens responsible for many infectious diseases and as such are the target of hygiene measures. Most microorganisms can reproduce and bacteria are able to exchange genes through conjugation and transduction between divergent species; the study of human physiology as a medical field originates in classical Greece, at the time of Hippocrates. Outside of Western tradition, early forms of physiology or anatomy can be reconstructed as having been present at around the same time in China and elsewhere.
Hippocrates incorporated his belief system called the theory of humours, which consisted of four basic substance: earth, water and fire. Each substance is known for having a corresponding humour: black bile, phlegm and yellow bile, respectively. Hippocrates noted some emotional connections to the four humours, which Claudius Galenus would expand on; the critical thinking of Aristotle and his emphasis on the relationship between structure and function marked the beginning of physiology in Ancient Greece. Like Hippocrates, Aristotle took to the humoral theory of disease, which consisted of four primary qualities in life: hot, cold and dry. Claudius Galenus, known as Galen of Pergamum, was the first to use experiments to probe the functions of the body. Unlike Hippocrates, Galen argued that humoral imbalances can be located in specific organs, including the entire body, his modification of this theory better equipped doctors to make more precise diagnoses. Galen played off of Hippocrates idea that emotions were tied to the humours, added the notion of temperaments: sanguine corresponds with blood.
Galen saw the human body consisting of three connected systems: the brain and nerves, which are responsible for thoughts and sensations.
Neurotransmitters are endogenous chemicals that enable neurotransmission. It is a type of chemical messenger which transmits signals across a chemical synapse, such as a neuromuscular junction, from one neuron to another "target" neuron, muscle cell, or gland cell. Neurotransmitters are released from synaptic vesicles in synapses into the synaptic cleft, where they are received by neurotransmitter receptors on the target cells. Many neurotransmitters are synthesized from simple and plentiful precursors such as amino acids, which are available from the diet and only require a small number of biosynthetic steps for conversion. Neurotransmitters play a major role in shaping everyday life and functions, their exact numbers are unknown, but more than 200 chemical messengers have been uniquely identified. Neurotransmitters are stored in synaptic vesicles, clustered close to the cell membrane at the axon terminal of the presynaptic neuron. Neurotransmitters are released into and diffuse across the synaptic cleft, where they bind to specific receptors on the membrane of the postsynaptic neuron.
Most neurotransmitters are about the size of a single amino acid. A released neurotransmitter is available in the synaptic cleft for a short time before it is metabolized by enzymes, pulled back into the presynaptic neuron through reuptake, or bound to a postsynaptic receptor. Short-term exposure of the receptor to a neurotransmitter is sufficient for causing a postsynaptic response by way of synaptic transmission. In response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. Low level "baseline" release occurs without electrical stimulation; the released neurotransmitter may move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way; this neuron may be connected to many more neurons, if the total of excitatory influences are greater than those of inhibitory influences, the neuron will "fire".
It will create a new action potential at its axon hillock to release neurotransmitters and pass on the information to yet another neighboring neuron. Until the early 20th century, scientists assumed that the majority of synaptic communication in the brain was electrical. However, through the careful histological examinations by Ramón y Cajal, a 20 to 40 nm gap between neurons, known today as the synaptic cleft, was discovered; the presence of such a gap suggested communication via chemical messengers traversing the synaptic cleft, in 1921 German pharmacologist Otto Loewi confirmed that neurons can communicate by releasing chemicals. Through a series of experiments involving the vagus nerves of frogs, Loewi was able to manually slow the heart rate of frogs by controlling the amount of saline solution present around the vagus nerve. Upon completion of this experiment, Loewi asserted that sympathetic regulation of cardiac function can be mediated through changes in chemical concentrations. Furthermore, Otto Loewi is credited with discovering acetylcholine —the first known neurotransmitter.
Some neurons do, communicate via electrical synapses through the use of gap junctions, which allow specific ions to pass directly from one cell to another. There are four main criteria for identifying neurotransmitters: The chemical must be synthesized in the neuron or otherwise be present in it; when the neuron is active, the chemical must produce a response in some target. The same response must be obtained. A mechanism must exist for removing the chemical from its site of activation. However, given advances in pharmacology and chemical neuroanatomy, the term "neurotransmitter" can be applied to chemicals that: Carry messages between neurons via influence on the postsynaptic membrane. Have little or no effect on membrane voltage, but have a common carrying function such as changing the structure of the synapse. Communicate by sending reverse-direction messages that affect the release or reuptake of transmitters; the anatomical localization of neurotransmitters is determined using immunocytochemical techniques, which identify the location of either the transmitter substances themselves, or of the enzymes that are involved in their synthesis.
Immunocytochemical techniques have revealed that many transmitters the neuropeptides, are co-localized, that is, one neuron may release more than one transmitter from its synaptic terminal. Various techniques and experiments such as staining and collecting can be used to identify neurotransmitters throughout the central nervous system. There are many different ways. Dividing them into amino acids and monoamines is sufficient for some classification purposes. Major neurotransmitters: Amino acids: glutamate, aspartate, D-serine, γ-aminobutyric acid, glycine Gasotransmitters: nitric oxide, carbon monoxide, hydrogen sulfide Monoamines: dopamine, epinephrine, serotonin Trace amines: phenethylamine, N-methylphenethylamine, tyramine, 3-iodothyronamine, tryptamine, etc. Peptides: oxytocin, substance P, cocaine and amphetamine regulated transcript, opioid peptides Purines: adenosine triphosphate, adenosine Catecholamines: dopamine, epinephrine Others: acetylcholine, etc. In addition, over 50 neuroactive pepti
Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by acting presynaptically via the inhibition of acetylcholine synthesis or release or by acting postsynaptically at the acetylcholine receptors of the motor nerve end-plate. While some drugs act presynaptically, those of current clinical importance work postsynaptically. In clinical use, neuromuscular block is used adjunctively to anesthesia to produce paralysis, firstly to paralyze the vocal cords, permit intubation of the trachea, secondly to optimize the surgical field by inhibiting spontaneous ventilation, causing relaxation of skeletal muscles; because the appropriate dose of neuromuscular-blocking drug may paralyze muscles required for breathing, mechanical ventilation should be available to maintain adequate respiration. Patients are still aware of pain after full conduction block has occurred. Quaternary ammonium muscle relaxants are quaternary ammonium salts used as drugs for muscle relaxation, most in anesthesia.
It is necessary to prevent spontaneous movement of muscle during surgical operations. Muscle relaxants inhibit neuron transmission to muscle by blocking the nicotinic acetylcholine receptor. What they have in common, is necessary for their effect, is the structural presence of quaternary ammonium groups two; some of them are found in nature and others are synthesized molecules. Neuromuscular blocking drugs are classified into two broad classes: Pachycurares, which are bulky molecules with nondepolarizing activity Leptocurares, which are thin and flexible molecules that tend to have depolarizing activity, it is common to classify them based on their chemical structure. Acetylcholine and decamethoniumSuxamethonium was synthesised by connecting two acetylcholine molecules and has the same number of heavy atoms between methonium heads as decamethonium. Just like acetylcholine, succinylcholine and other polymethylene chains, of the appropriate length and with two methonium, heads have small trimethyl onium heads and flexible links.
They all exhibit a depolarizing block. Aminosteroids Pancuronium, rocuronium, dacuronium, malouètine, dipyrandium, chandonium, HS-342 and other HS- compounds are aminosteroidal agents, they have in common the steroid structural base, which provides a bulky body. Most of the agents in this category would be classified as non-depolarizing. Tetrahydroisoquinoline derivativesCompounds based on the tetrahydroisoquinoline moiety such as atracurium and doxacurium would fall in this category, they have a long and flexible chain between the onium heads, except for the double bond of mivacurium. D-tubocurarine and dimethyltubocurarine are in this category. Most of the agents in this category would be classified as non-depolarizing. Gallamine and other chemical classesGallamine is a trisquaternary ether with three ethonium heads attached to a phenyl ring through an ether linkage. Many other different structures have been used for their muscle relaxant effect such as alcuronium, diadonium and tropeinium. Novel NMB agentsIn recent years much research has been devoted to new types of quaternary ammonium muscle relaxants.
These are asymmetrical diester isoquinolinium compounds and bis-benzyltropinium compounds that are bistropinium salts of various diacids. These classes have been developed to create muscle relaxants that are shorter acting. Both the asymmetric structure of diester isoquinolinium compounds and the acyloxylated benzyl groups on the bisbenzyltropiniums destabilizes them and can lead to spontaneous breakdown and therefore a shorter duration of action; these drugs fall into two groups: Non-depolarizing blocking agents: These agents constitute the majority of the clinically relevant neuromuscular blockers. They act by competitively blocking the binding of ACh to its receptors, in some cases, they directly block the ionotropic activity of the ACh receptors. Depolarizing blocking agents: These agents act by depolarizing the sarcolemma of the skeletal muscle fiber; this persistent depolarization makes the muscle fiber resistant to further stimulation by ACh. A neuromuscular non-depolarizing agent is a form of neuromuscular blocker that does not depolarize the motor end plate.
The quaternary ammonium muscle relaxants belong to this class. Below are some more common agents that act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors. Tubocurarine, found in curare of the South American plant Pareira, Chondrodendron tomentosum, is the prototypical non-depolarizing neuromuscular blocker, it has a long duration of action. Side-effects include hypotension, explained by its effect of increasing histamine release, a vasodilator, as well as its effect of blocking autonomic ganglia, it is excreted in the urine. This drug needs to block about 70–80% of the ACh receptors for neuromuscular conduction to fail, hence for effective blockade to occur. At this stage, end-plate potentials can still be detected, but are too small to reach the threshold potential needed for activation of muscle fiber contraction. A depolarizing neuromuscular blocking agent is a form of neuromuscular blocker that depolarizes the motor end plate. An example is succinylcholine.
Depolarizing blocking agents work by depolarizing the plasma membrane of the muscle fiber, similar to acetylcholine. Ho
Suxamethonium chloride known as suxamethonium or succinylcholine, is a medication used to cause short-term paralysis as part of general anesthesia. This is done to help with tracheal electroconvulsive therapy, it is given either by injection into a muscle. When used in a vein onset of action is within one minute and effects last for up to 10 minutes. Common side effects include low blood pressure, increased saliva production, muscle pain, rash. Serious side effects include allergic reactions, it is not recommended in people who are at a history of myopathy. Use during pregnancy appears to be safe for the baby. Suxamethonium is of the depolarizing type, it works by blocking the action of acetylcholine on skeletal muscles. Suxamethonium was described as early as 1906 and came into medical use in 1951, it is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Suxamethonium is available as a generic medication; the wholesale cost in the developing world is about US$0.45 to US$1.31 a dose.
It may colloquially be referred to as "sux". Its medical uses are limited to short-term muscle relaxation in anesthesia and intensive care for facilitation of endotracheal intubation, it is perennially popular in emergency medicine because it has the fastest onset and shortest duration of action of all muscle relaxants. The former is a major point of consideration in the context of trauma care, where endotracheal intubation may need to be completed quickly; the latter means that, should attempts at endotracheal intubation fail and the person cannot be ventilated, there is a prospect for neuromuscular recovery and the onset of spontaneous breathing before low blood oxygen levels occurs. It may be better than rocuronium in people without contraindications due to its faster onset of action and shorter duration of action. Suxamethonium is commonly used as the sole muscle relaxant during electroconvulsive therapy, favoured for its short duration of action. Suxamethonium is degraded by plasma butyrylcholinesterase and the duration of effect is in the range of a few minutes.
When plasma levels of butyrylcholinesterase are diminished or an atypical form is present, paralysis may last much longer, as is the case in liver failure or in neonates. It is recommended that the vials be stored for optimum action; this is all the more important in temperate and tropical countries where room temperatures can go as high as 30 °C. Side effects include malignant hyperthermia, muscle pains, acute rhabdomyolysis with high blood levels of potassium, transient ocular hypertension and changes in cardiac rhythm, including slow heart rate, cardiac arrest. In people with neuromuscular disease or burns, an injection of suxamethonium can lead to a large release of potassium from skeletal muscles resulting in cardiac arrest. Conditions having susceptibility to suxamethonium-induced high blood potassium are burns, closed head injury, Guillain–Barré syndrome, cerebral stroke, severe intra-abdominal sepsis, massive trauma and tetanus. Suxamethonium does not produce unconsciousness or anesthesia, its effects may cause considerable psychological distress while making it impossible for a patient to communicate.
Therefore, administration of the drug to a conscious patient is contraindicated. The side effect of high blood potassium may occur because the acetylcholine receptor is propped open, allowing continued flow of potassium ions into the extracellular fluid. A typical increase of potassium ion serum concentration on administration of suxamethonium is 0.5 mmol per liter. The increase is transient in otherwise healthy patients; the normal range of potassium is 3.5 to 5 mEq per liter. High blood potassium does not result in adverse effects below a concentration of 6.5 to 7 mEq per liter. Therefore, the increase in serum potassium level is not catastrophic in otherwise healthy patients. High blood levels of potassium will cause changes in cardiac electrophysiology, which, if severe, can result in asystole. Malignant hyperthermia from suxamethonium administration can result in a drastic and uncontrolled increase in skeletal muscle oxidative metabolism; this overwhelms the body's capacity to supply oxygen, remove carbon dioxide, regulate body temperature leading to circulatory collapse and death if not treated quickly.
Susceptibility to malignant hyperthermia is inherited as an autosomal dominant disorder, for which there are at least six genetic loci of interest, the most prominent being the ryanodine receptor gene. MH susceptibility is phenotype and genetically related to central core disease, an autosomal dominant disorder characterized both by MH symptoms and by myopathy. MH is unmasked by anesthesia, or when a family member develops the symptoms. There is no straightforward test to diagnose the condition; when MH develops during a procedure, treatment with dantrolene sodium is initiated. The normal short duration of action of suxamethonium is due to the rapid metabolism of the drug by non-specific plasma cholinesterases; however plasma cholinesterase activity is reduced in some people due to either genetic variation or acquired conditions, which results in a prolonged duration of neuromuscular block. Genetically, ninety six percent of the population have a normal genotype and block d
Endothelium refers to cells that line the interior surface of blood vessels and lymphatic vessels, forming an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. It is a thin layer of single-layered, squamous cells called endothelial cells. Endothelial cells in direct contact with blood are called vascular endothelial cells, whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries; these cells have unique functions in vascular biology. These functions include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, neutrophil recruitment, hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. Endothelium is mesodermal in origin. Both blood and lymphatic capillaries are composed of a single layer of endothelial cells called a monolayer. In straight sections of a blood vessel, vascular endothelial cells align and elongate in the direction of fluid flow.
The foundational model of anatomy makes a distinction between endothelial cells and epithelial cells on the basis of which tissues they develop from, states that the presence of vimentin rather than keratin filaments separate these from epithelial cells. Many considered the endothelium a specialized epithelial tissue. Endothelial cells are involved in many aspects of vascular biology, including: Barrier function - the endothelium acts as a semi-selective barrier between the vessel lumen and surrounding tissue, controlling the passage of materials and the transit of white blood cells into and out of the bloodstream. Excessive or prolonged increases in permeability of the endothelial monolayer, as in cases of chronic inflammation, may lead to tissue edema/swelling. Blood clotting; the endothelium provides a non-thrombogenic surface because it contains, for example, heparan sulfate which acts as a cofactor for activating antithrombin, a protease that inactivates several factors in the coagulation cascade.
Inflammation Formation of new blood vessels Vasoconstriction and vasodilation, hence the control of blood pressure Repair of damaged or diseased organs via an injection of blood vessel cells Angiopoietin-2 works with VEGF to facilitate cell proliferation and migration of endothelial cells Endothelial dysfunction, or the loss of proper endothelial function, is a hallmark for vascular diseases, is regarded as a key early event in the development of atherosclerosis. Impaired endothelial function, causing hypertension and thrombosis, is seen in patients with coronary artery disease, diabetes mellitus, hypercholesterolemia, as well as in smokers. Endothelial dysfunction has been shown to be predictive of future adverse cardiovascular events, is present in inflammatory disease such as rheumatoid arthritis and systemic lupus erythematosus. One of the main mechanisms of endothelial dysfunction is the diminishing of nitric oxide due to high levels of asymmetric dimethylarginine, which interfere with the normal L-arginine-stimulated nitric oxide synthesis and so leads to hypertension.
The most prevailing mechanism of endothelial dysfunction is an increase in reactive oxygen species, which can impair nitric oxide production and activity via several mechanisms. The signalling protein ERK5 is essential for maintaining normal endothelial cell function. A further consequence of damage to the endothelium is the release of pathological quantities of von Willebrand factor, which promote platelet aggregation and adhesion to the subendothelium, thus the formation of fatal thrombi. Anatomy photo: Circulatory/vessels/capillaries1/capillaries3 - Comparative Organology at University of California, Davis, "Capillaries, non-fenestrated" Histology image: 21402ooa – Histology Learning System at Boston University Endothelium Journal of Endothelial Cell Research, Informa Healthcare Endothelium and inflammation Platelet Activation, University of Washington
Membrane potential is the difference in electric potential between the interior and the exterior of a biological cell. With respect to the exterior of the cell, typical values of membrane potential given in millivolts, range from –40 mV to –80 mV. All animal cells are surrounded by a membrane composed of a lipid bilayer with proteins embedded in it; the membrane serves as a diffusion barrier to the movement of ions. Transmembrane proteins known as ion transporter or ion pump proteins push ions across the membrane and establish concentration gradients across the membrane, ion channels allow ions to move across the membrane down those concentration gradients. Ion pumps and ion channels are electrically equivalent to a set of batteries and resistors inserted in the membrane, therefore create a voltage between the two sides of the membrane. All plasma membranes have an electrical potential across them, with the inside negative with respect to the outside; the membrane potential has two basic functions.
First, it allows a cell to function as a battery, providing power to operate a variety of "molecular devices" embedded in the membrane. Second, in electrically excitable cells such as neurons and muscle cells, it is used for transmitting signals between different parts of a cell. Signals are generated by opening or closing of ion channels at one point in the membrane, producing a local change in the membrane potential; this change in the electric field can be affected by either adjacent or more distant ion channels in the membrane. Those ion channels can open or close as a result of the potential change, reproducing the signal. In non-excitable cells, in excitable cells in their baseline states, the membrane potential is held at a stable value, called the resting potential. For neurons, typical values of the resting potential range from –70 to –80 millivolts; the opening and closing of ion channels can induce a departure from the resting potential. This is called a depolarization if the interior voltage becomes less negative, or a hyperpolarization if the interior voltage becomes more negative.
In excitable cells, a sufficiently large depolarization can evoke an action potential, in which the membrane potential changes and for a short time reversing its polarity. Action potentials are generated by the activation of certain voltage-gated ion channels. In neurons, the factors that influence the membrane potential are diverse, they include numerous types of ion channels, some of which are chemically gated and some of which are voltage-gated. Because voltage-gated ion channels are controlled by the membrane potential, while the membrane potential itself is influenced by these same ion channels, feedback loops that allow for complex temporal dynamics arise, including oscillations and regenerative events such as action potentials; the membrane potential in a cell derives from two factors: electrical force and diffusion. Electrical force arises from the mutual attraction between particles with opposite electrical charges and the mutual repulsion between particles with the same type of charge.
Diffusion arises from the statistical tendency of particles to redistribute from regions where they are concentrated to regions where the concentration is low. Voltage, synonymous with difference in electrical potential, is the ability to drive an electric current across a resistance. Indeed, the simplest definition of a voltage is given by Ohm's law: V=IR, where V is voltage, I is current and R is resistance. If a voltage source such as a battery is placed in an electrical circuit, the higher the voltage of the source the greater the amount of current that it will drive across the available resistance; the functional significance of voltage lies only in potential differences between two points in a circuit. The idea of a voltage at a single point is meaningless, it is conventional in electronics to assign a voltage of zero to some arbitrarily chosen element of the circuit, assign voltages for other elements measured relative to that zero point. There is no significance in which element is chosen as the zero point—the function of a circuit depends only on the differences not on voltages per se.
However, in most cases and by convention, the zero level is most assigned to the portion of a circuit, in contact with ground. The same principle applies to voltage in cell biology. In electrically active tissue, the potential difference between any two points can be measured by inserting an electrode at each point, for example one inside and one outside the cell, connecting both electrodes to the leads of what is in essence a specialized voltmeter. By convention, the zero potential value is assigned to the outside of the cell and the sign of the potential difference between the outside and the inside is determined by the potential of the inside relative to the outside zero. In mathematical terms, the definition of voltage begins with the concept of an electric field E, a vector field assigning a magnitude and direction to each point in space. In many situations, the electric field is a conservative field, which means that it can be expressed as the gradient of a scalar function V, that is, E = –∇V.
This scalar field V is referred to as the voltage distribution. Note that the definition allows for an arbitrary constant of integration—this is why absolute values of voltage are not meaningful. In general, electric fields can be treated as