Membrane diffusion active

Materials may be absorbed by a variety of mechanisms. Depending on the nature of the material and the site of absorption, there may be passive diffusion, filtration processes, faciHtated diffusion, active transport and the formation of microvesicles for the cell membrane (pinocytosis) (61). EoUowing absorption, materials are transported in the circulation either free or bound to constituents such as plasma proteins or blood cells. The degree of binding of the absorbed material may influence the availabiHty of the material to tissue, or limit its elimination from the body (excretion). After passing from plasma to tissues, materials may have a variety of effects and fates, including no effect on the tissue, production of injury, biochemical conversion (metaboli2ed or biotransformed), or excretion (eg, from liver and kidney). 

The membranes of nerve cells contain well-studied ion channels that are responsible for the action potentials generated across the membrane. The activity of some of these channels is controlled by neurotransmitters hence, channel activity can be regulated. One ion can regulate the activity of the channel of another ion. For example, a decrease of Ca + concentration in the extracellular fluid increases membrane permeability and increases the diffusion of Na+. This depolarizes the membrane and triggers nerve discharge, which may explain the numbness, tinghng, and muscle cramps symptomatic of a low level of plasma Ca. ... 

PLASMA MEMBRANES ARE INVOLVED IN FACILITATED DIFFUSION, ACTIVE TRANSPORT, OTHER PROCESSES... 

In addition to faster solute transport rates, the major experimental features of membrane-facilitated transport that distinguish it from membrane diffusion include (1) specificity and selectivity (2) saturability (3) inhibition, activation, and cooperativity (4) transmembrane effects and (5) greater temperature sensitivity than is characteristic of membrane diffusion [42],... 

Two distinguishing features of gastrointestinal active and facilitated transport processes are that they are capacity-limited and inhibitable. Passive transcellular solute flux is proportional to mucosal solute concentration (C), where the proportionality constant is the ratio of the product of membrane diffusion coefficient (Dm) and distribution coefficient (Kd) to the length of the transcellular pathway (Lm). 

Figure 1 General pathways through which molecules can actively or passively cross a monolayer of cells. (A) Endocytosis of solutes and fusion of the membrane vesicle with the opposite plasma membrane in an active process called transcytosis. (B) Similar to A, but the solute associates with the membrane via specific (e.g., receptor) or nonspecific (e.g., charge) interactions. (C) Passive diffusion between the cells through the paracellular space. (C, C") Passive diffusion (C ) through the cell membranes and cytoplasm or (C") via partitioning into and lateral diffusion within the cell membrane. (D) Active or carrier-mediated transport of an otherwise poorly membrane permeable solute into and/or out of a cellular barrier.

Dense membranes are used for pervaporation, as for reverse osmosis, and the process can be described by a solution-diffusion model. That is, in an ideal case there is equilibrium at the membrane interfaces and diffusional transport of components through the bulk of the membrane. The activity of a component on the feed side of the membrane is proportional to the composition of that component in the feed solution. 

Buccal dosage forms can be of the reservoir or the matrix type. Formulations of the reservoir type are surrounded by a polymeric membrane, which controls the release rate. Reservoir systems present a constant release profile provided (1) that the polymeric membrane is rate limiting, and (2) that an excess amoimt of drug is present in the reservoir. Condition (1) may be achieved with a thicker membrane (i.e., rate controlling) and lower diffusivity in which case the rate of drug release is directly proportional to the polymer solubility and membrane diffusivity, and inversely proportional to membrane thickness. Condition (2) may be achieved, if the intrinsic thermodynamic activity of the drug is very low and the device has a thick hydrodynamic diffusion layer. In this case the release rate of the drug is directly proportional to solution solubility and solution diffusivity, and inversely proportional to the thickness of the hydrodynamic diffusion layer. 

For single-component gas permeation through a microporous membrane, the flux (J) can be described by Eq. (10.1), where p is the density of the membrane, ris the thermodynamic correction factor which describes the equilibrium relationship between the concentration in the membrane and partial pressure of the permeating gas (adsorption isotherm), q is the concentration of the permeating species in zeolite and x is the position in the permeating direction in the membrane. Dc is the diffusivity corrected for the interaction between the transporting species and the membrane and is described by Eq. (10.2), where Ed is the diffusion activation energy, R is the ideal gas constant and T is the absolute temperature. 

Inorganic ions, such as sodium and potassium, move through the cell membrane by active transport. Unlike diffusion, energy is required for active transport as the chemical is moving from a lower concentration to a higher one. One example is the sodium-potassium ATPase pump, which transports sodium [Na ] ions out of the cell and potassium [K ] into the cell. 

Drugs and other substances that pass through biologic membranes usually do so via passive diffusion, active transport, facilitated diffusion, or some special process such as endocytosis (Fig. 2-2). Each of these mechanisms is discussed here. 

Methods of estimating diffusion coefficients originate with the earlier studies of gas transport in semipermeable membranes. Diffusion can be treated as a thermally activated process, the temperature dependence of which is given by an Arrhenius type of equation (Equation 4). The activation energy (E.) is a constant for a polymer/dif-fusant combination,... 

The simplest of these functions is that of a permeability barrier that limits free diffusion of solutes between the cytoplasm and external environment. Although such barriers are essential for cellular life to exist, there must also be a mechanism by which selective permeation allows specific solutes to cross the membrane. In contemporary cells, such processes are carried out by transmembrane proteins that act as channels and transporters. Examples include the proteins that facilitate the transport of glucose and amino acids into the cell, channels that allow potassium and sodium ions to permeate the membrane, and active transport of ions by enzymes that use ATP as an energy source. 

Other processes that lead to nonlinear compartmental models are processes dealing with transport of materials across cell membranes that represent the transfers between compartments. The amounts of various metabolites in the extracellular and intracellular spaces separated by membranes may be sufficiently distinct kinetically to act like compartments. It should be mentioned here that Michaelis-Menten kinetics also apply to the transfer of many solutes across cell membranes. This transfer is called facilitated diffusion or in some cases active transport (cf. Chapter 2). In facilitated diffusion, the substrate combines with a membrane component called a carrier to form a carrier-substrate complex. The carrier-substrate complex undergoes a change in conformation that allows dissociation and release of the unchanged substrate on the opposite side of the membrane. In active transport processes not only is there a carrier to facilitate crossing of the membrane, but the carrier mechanism is somehow coupled to energy dissipation so as to move the transported material up its concentration gradient. 

The permeability of compounds through cell membranes is of great interest and importance for the elucidation of many biologic ceU functions. Most metabolically important substances are transported across membranes by active transport. Many other intrinsic compounds, as well as most drugs, are known to pass the membrane by passive diffusion. 

All exposure pathways can ultimately result in the absorption of soluble substances across the body s membranes (skin, eyes, respiratory, or digestive tracts), by passive or active diffusion, active transport, or cellular pinocytosis/phagocytosis (the engulfment of foreign particles by cells). The proportion of a substance in contact with a membrane that is absorbed is a complex function of many factors, including the concentration and chemical form of the substance, the relative chemical conditions ambient on either side of the membrane, and the surface area of the membrane with which the substance is in contact. 

Keywords Active transport Adsoiptive endocytosis and transcytosis Brain endothelial cell Cytokine Endothelin Facilitated diffusion Inmiune cell Neurovascular unit Trans-membrane diffusion... 

ACh is found to be stored within the terminals of motor neurons. Detailed analysis has demonshated that ACh is stored within small packages called synaptic vesicles that are concenhated around active zones on the presynaptic membrane. These active zones have been identified as specialized sites for neurohansmitter containing vesicle release. The enzyme for synthesizing ACh from choline and acetyl-Co A, choline acetyl transferase, is also found within the presynaptic terminal. Choline acetyl transferase is found in the cytoplasm. When ACh is synthesized it is pumped into synaptic vesicles by means of a specific carrier molecule located in the vesicle membrane. Once released, ACh subsequently diffuses across the synapse and activates nicotinic ACh receptors localized on the plasma membrane of the postsynapdc muscle cell producing depolarization of the muscle (see below). 

The mode of transport through a membrane may be passive, active, or facilitated type. In passive transport, the membrane acts as a barrier and permeation of the components is determined by their diffusivity and concentration in the membrane or just by their size. In facilitated transport along with the chemical potential gradient, the mass transport is coupled to specific carrier components in the membrane. In active transport driving force for transport is achieved by a chemical reaction in the membrane phase. 

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