Cell membrane Potential barrier

In addition to the differences in phospholipid content between microbial and host cell membranes, it has been demonstrated that disparity exists between the transmembrane potentials of both organisms. The transmembrane potential is defined by the proton flux between the inner and outer bilayers of the cytoplasmic membrane and ranges from —90 to —110 mV in normal mammalian cells in contrast to transmembrane potentials of —130 to —150mV for logarithmic phase microbes. The differences in these electrochemical gradients have been postulated to drive the influx of peptides into the cell and thus act as a crucial barrier for defining host defense peptide selectivity. ... 

By virtue of their size and charge, peptide molecules are not the ideal candidates for transfer into the systemic circulation following instillation in the nose. Among the many barriers to absorption that must be overcome are mucociliary clearance, extracellular enzymatic destruction, the lipophilic bilayer membrane of nasal epithelial cells, the potential for nasal epithelial cells to degrade any peptide molecules that cross the lipid bilayer, and the potential to establish futile cycles of endocytosis and exocytosis on the apical surface of polarized epithelial cells. Indeed, in the face of these multiple barriers, it seems all the more remarkable that any substantial absorption of peptide drugs from the nose has ever been observed. Despite these barriers, recent... 

The barrier to paracellular diffusion potentially isolates the brain from many essential polar nutrients such as glucose and amino acids that are required for metabolism and, therefore, the BBB endothelium must contain a number of specific solute carriers (transporters) to supply the CNS with its requirements for these substances. The formation of tight junctions essentially confers on the BBB the properties of a continuous cell membrane, both in terms of the diffusional characteristics imposed by the lipid bilayer, and the directionality and properties of the specific transport proteins, and solute carriers (SLC) that are present in the cell membrane. Examples of BBB solute carriers (SLC transporters) are listed in Table 27.2. 

Due to their highly biocompatible nature, dendritic PGs have a broad range of potential applications in medicine and pharmacology. The versatility of the polyglycerol scaffolds for application in the biomedical field has recently been reviewed [131], and a number of examples were described, therein, e.g., smart and stimuli-responsive delivery and release of bioactive molecules, enhanced solubilization of hydrophobic compounds, surface-modification and regenerative therapy, as well as transport of active agents across biological barriers (cell-membranes, tumor tissue, etc.). 

Notably, all these characteristic alterations are conferred by cell membranes particularly the cytoplasmic membrane that is basically a lipid-bilayer structure imbedded with certain proteins. The lipid-bilayer forms a barrier to surround and protect the cell contents and the transmembrane proteins are responsible for the cell communications with the environment. For example, receptor proteins mediate the growth signals produced by growth factors and mitogens and any other stimuli. Ion channel proteins control the flux of ions across the cytoplasmic membrane to regulate membrane potential, osmolar-ity (or cell volume), etc. 

We begin by showing how active transport can directly affect membrane potentials. We then compare the temperature dependencies of metabolic reactions with those for diffusion processes across a barrier to show that a marked enhancement of solute influx caused by increasing the temperature does not necessarily indicate that active transport is taking place. Next we will consider a more reliable criterion for deciding whether fluxes are passive or not — namely, the Ussing-Teorell, or flux ratio, equation. We will then examine a specific case in which active transport is involved, calculate the energy required, and finally speculate on why K+ and Cl- are actively transported into plant cells and Na+ is actively transported out. 

The transfer of the information described in the preceding sections of this chapter to the in vivo situation is a matter where opinions are sharply divided, even if more than 20 years have elapsed since the discovery by Vasington and Murphy [4]. One key problem, naturally, is the impossibility of reproducing the composition and the conditions of the cytosol in in vitro experiments. The above mentioned effect of Mg on the rate of Ca influx into mitochondria is but one striking example of the difficulties inherent to the extrapolation to the in situ conditions. Of interest in this respect are recent experiments [124,125] in which methods have been devised to estimate simultaneously the membrane potential across the plasma membrane and the mitochondria of nerve endings in situ. The conclusion of this work has been that the concentration of free Ca in the cytosol correlates directly to the membrane potential across the mitochondrial membrane, and is maintained at a steady-state level below 1 jaM. Simulation of the in situ conditions has also been the aim of studies [126] in which isolated liver endoplasmic reticulum has been added to media in which isolated liver mitochondria were made to take up Ca, or in which liver cells have been treated with digitonin to abolish the permeability barrier of the plasma membrane. It was found that respiring mitochondria lower the external Ca " concentration to about 0.5 /iM. The addition of endoplasmic reticulum vesicles produces a further decrease of the external Ca " to about 0.2 jaM. Thus, mitochondria... 

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