Intercellular channels

The total swelling time for a dried SPH in aqueous solution is determined by two factors q and t2- h is the time for water to reach all the surface of the pores in the SPHs. It is determined by the effectiveness of the capillary action in a SPH. 2 is the actual swelling time of the polymer matrix, which is determined by the thickness of the cell walls and struts. Because the cell walls and stints of SPHs are very thin, they have very short characteristic swelling times. For SPHs, t2 is comparable to that of a ultrathin hydrogel film. The capillary action is mainly determined by the availability of capillary channels and the wettability of the channels. Various approaches have been attempted to maintain good capillary action (i.e., to decrease q) by maintaining open intercellular channels and good surface wettability. 

Heart muscle fibers are coupled by gap junctions. These intercellular channels provide the exchange of small molecules (<1,000 D), like second messengers, between the cells and they allow electrical coupling. Thus, these cells connected to each other form a syncytium. However, from mapping studies it became evident that under certain conditions, e.g. regional ischemia, the ischemic region uncouples. In addition, mapping studies demonstrated that there is a special activation pattern which accounts for a directed activation of the whole heart. This activation pattern exhibits a considerable similarity from beat to beat. It is well known that the conduction velocity varies between... 

Gap junctions are formed from hexagonal arrays of a rod-shaped protein. Arrays in the membranes of adjacent cells line up to form intercellular channels that can transmit small molecules from cell to cell in some tissues. (Source Adapted from L. Makowski, D. L. D. Caspar, W. C. Phillips, and D. A. Goodenough, Gap junction structures. II. Analysis of the x-ray diffraction data,./. Cell Biol. 74 629, 1977.)... 

Variation in hormonal levels (especially in estrogens) during the menstrual cycle determines the alteration of epithelial cell thickness, causing the widening of the intercellular channels and consequently variation in pH, composition, and secretion amount. Moreover, hormonal changes influence enzymatic activity of endopeptidases and aminopeptidases, causing further complications for drug delivery and therapeutic schedule [2,3,5,6,10],... 

The principal routes of penetration are thus transcellular and intercellular. Currently there is considerable debate as to which of these predominates. Work with esters of nicotinic acid has shown that the intercellular channels are significant [5.] and considerable effort is being conducted to identify their exact nature and role. Microscopic examination shows that they contain structured lipids the chemical nature of which is complex [6J. Cholesterol esters, cerebrosides and sphingomyelins are present in association with other lipids in smaller concentrations. It is likely that the main barrier to skin penetration resides in the channels and that a diffusing drug molecule experiences a lipid environment which has considerable structure. Penetration enhancers may act by temporarily altering the nature of the structured lipids, perhaps by lowering their normal phase transition temperature which occurs around 38°C. 

An important aspect of the epithelium is an elaborate system of channels between the cells. These intercellular channels are capable of changing width as the hormone levels change during the menstrual cycle. The channels can accommodate rapid movement of leukocytes and large proteins such as IgG and albumin they are an important pathway of watery secretion from the blood network to the tissue. 

During the late follicular phase, estrogen stimulates mitosis in the basal and parabasal layers. This proliferation of cells leads to an increase in epithelial thickness, as well as in the number of layers (Figure 11.2). A parallel increase in the number of intercellular junctions renders the epithelium more cohesive. The number of desmosomes increases approximately 10-fold from the early to late follicular phase. The intercellular channels are narrow during the late follicular phase. Thus in this phase, the epithelium is thick, tight and cohesive. 

During the luteal phase, desquamation (shedding) occurs on the superficial epithelial layer, extending as far as the intermediate cells. The vaginal surface loses its intact structure and the epithelium becomes loose and porous. This cyclic desquamation is preceded by loosening of intercellular grooves, as well as a porelike widening of the intercellular channels. Thus in this phase, the epithelium is thin, loose and porous. 

The hydrophilic form is absorbed mainly through pore-like pathways such as the intercellular channels and thus is highly dependent on the stage of the cycle, with greater absorption occuring when the interceullular channels are wide and porous. 

Dry vagina the bioadhesive gel can hydrate vaginal tissue for 3-4 days after a single application. Tissue hydration is caused by an increased blood flow, thus increasing transudation of vaginal fluid though the intercellular channels of the vaginal epithelium. 

Which of the following do not leak through the intercellular channels of vaginal epithelium at the late luteal phase and early follicular phase (a) erythrocytes, (b) IgG, (c) albumin, (d) leukocytes. 

Structured lipid bilayers within intercellular channels... 

Gap junctions provide in the nervous system the structural correlate of one class of electrical synapses, characterized by very close apposition between the presynaptic and postsynaptic membranes. It should be noted, in this respect, that different junctional specializations can mediate different forms of electrical transmission between neurons (Bennett, 1997). Electrical synapses transmit preferentially, but not exclusively, low-frequency stimuli, that allow the rapid transfer of a presynaptic impulse into an electrical excitatory potential in the postjunctional cells. Electrical transmission, via the intercellular channels, can be bidirectional. The widely held opinion that electrical transmission is characteristic of lower vertebrates probably derives from the large cell systems in which electrical synapses were identified in the initial period of intracellular recording (reviewed by Bennett, 1997). Contradicting this view, electrotonic coupling between neurons has now been demonstrated in many areas of the mammalian central nervous system and has been implicated in neuronal synchronization. Gap junctional intercellular communication can occur between glial cells, glia and neurons, as well as between neurons. 

Figure 10-14 Ion and fluid movement in the nonpigmented ciliary epithelium. Na+ enters the nonpigmented ciliary epithelium from the stromal side either by diffusion or by NaVH+ exchange. Na+, the main cation involved in aqueous formation, is transported extraceUularly into the lateral intercellular channel by a Na+-K+-adenosine triphosphatase-dependent transport system. HC03 forms from the hydration of CO2, a reaction catalyzed by carbonic anhydrase. HC03", the major anion involved in aqueous formation, balances a portion of the Na+ being transported into the lateral intercellular channel. Cl" enters the intercellular space by a mechanism that is not understood. This movement of ions into the lateral intercellular space creates a hypertonic fluid, and water enters by osmosis. Because of the restriction on the stromal side of the channel, the newly formed fluid moves toward the posterior chamber. A rapid diffusional exchange of CO2 allows for its movement into the posterior chamber. (Adapted from Cole DF. Secretion of aqueous humor. Exp Eye Res 1977 25(suppl) l6l-176.)...

Syncytium (pL, syncytia) A tissue in which the intracellular spaces of adjacent cells are coupled through intercellular channels, so that current can pass between any two intracellular points without crossing the cell membrane. 

Gap junctions are aggregates of intercellular channels, formed by head-to-head alignment of two he-michaimels (connections), each of which is made up of six coimexin protein molecules (Harold et al. 1997). Zhang etal. (1999) demonstrated that hypoxia-reoxygenation induced a temporal reduction of gap junctional intercellular communication in human umbihcal vein endothelial cells and that the protein tyrosine kinase pathway was primarily responsible for this gap junctional intercellular communication abnormality. 

To record the activity of intercellular channels, pulses, and more frequently DC voltages, were delivered to Cell 1 after voltage clamping of both cells as described above. These procedures produced flickering (multiple current activities) in the intercellular channels of both cells (ii and 12), which were of similar amplitudes and opposite polarities. Inward channel currents in one coupled cell were taken as the ij currents. The intercellular junctional conductance of channels (microconductance or gj) was calculated as ij/Vj. 

In other tissues, many junction channels are present between coupled cells. Numbers vary from very few to hundreds or thousands. Furthermore, the nature of the connexins surrounding the intercellular pores is variable. In many instances there are hybrid channels (different connexins in one charmel) or charmels of different nature within one junction (24). This is important to understand the effects of different stimuli on intercellular coupling since a given stimulus does not necessarily act in identical form on different connexins. Furthermore, intercellular channels do not behave in an all-or-none manner since some may be totally or partially open as well as totally or partially closed. 

Figure 5 Effect of 1 mM Na-dithionite on intercellular channel currents, (a) control activity and (b) during superfusion with dithionite. Note deflections of equal amplitude and opposite polarity. In squares, cell numbers. Numbers at bottom indicate experimental parameters.

The supercritical solvent is absorbed by the solid matrix changing the cellular structure thickness and reducing its membrane resistance, which leads to an increase in the diameter of intercellular channels thus reducing the resistance to mass transfer ... 

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