Intracellular environment

Ion Channels. The excitable cell maintains an asymmetric distribution across both the plasma membrane, defining the extracellular and intracellular environments, as well as the intracellular membranes which define the cellular organelles. This maintained a symmetric distribution of ions serves two principal objectives. It contributes to the generation and maintenance of a potential gradient and the subsequent generation of electrical currents following appropriate stimulation. Moreover, it permits the ions themselves to serve as cellular messengers to link membrane excitation and cellular... 

Cisplatin was discovered fortuitously by observing that bacteria present in electrolysis solutions could not divide. It is hypothesized that in the intracellular environment, a chloride is lost and replaced by a water molecule. The resulting species is an efficient bifunctional interactor with DNA, forming platinum-based cross-links similar to that formed by alkylating agents. 

A series of bathing solutions mimicking the intracellular environment in fatigued muscle have been studied by Godt and Nosek (1989). Variations in ATP, ADP, PCr, and Cr contents had only marginal effects on the tension development compared to decreases in pH and increases in Pj. 

Cells are normally kept at osmotic (water activity) equilibrium by the action of the Na-pump. Inhibition of the pump with the specific Na -K -ATPase inhibitor, ouabain, causes cell swelling as does inhibition of it by hypothermia. The intracellular environment contains a high concentration of K (100 to 120 mM, in most mammalian cells), lower concentrations of Na (about 10 to 30 mM), and high... 

R. Grima and S. Schnell, A systematic investigation of the rate laws valid in intracellular environments, Biophys. Chem. 124, 1 (2006). 

S. Schnell and T. E. Turner, Reaction kinetics in intracellular environments with macromolecular crowding simulations and rate laws, Prog. Biophys. Mol. Biol. 85, 235 (2004). 

A prerequisite for this model is the existence of both external and internal gates, i.e., protein domains that are capable of occluding access to the substrate binding site from the extracellular and intracellular environment, respectively. Little is known about such domains in this family of transporters. The molecular mechanisms governing the cooperative function of the putative gating domains also remain unknown. It could be predicted, however, that stabilization of the transporter in the outward-facing conformation in the absence of substrate but in the presence of Na+ requires a network of con-... 

The intracellular environment of eukaryote cells can be subdivided into many regions, including the organelles, nucleus, cytoplasm and the cell periphery. Thus solutes must be delivered to the right intracellular compartment at the correct time to efficiently serve cellular biochemistry. Uncharged solutes such as glucose presumably diffuse across the cell, and the traditional view held until recently was that the major electrolytes, such as Na+,K+,CF and Mg2+, also move around the cell by simple diffusion to eventually arrive at the relevant subcellular compartment by chance. 

Chen AK, Cheng ZL, Behlke MA, Tsourkas A (2008) Assessing the sensitivity of commercially available fluorophores to the intracellular environment. Anal Chem 80 7437-7444... 

The plasma membrane forms a boundary between the extra- and intracellular environments whereas membranes within a cell form boundaries between the organelles and the cytosol. These are discussed in other chapters, whereas the material in this chapter focuses on the plasma membrane. A primary function of this membrane is to serve as a barrier to prevent the entry of some molecules and ions into the cell and to retain others within the cell (Table 5.1). The plasma membrane has other roles, which are related to the presence of proteins within or attached to the membrane. These are ... 

To provide a source of polyunsaturated fatty acids and other compounds that can be released to act as intracellular messengers or as precursors for such messengers. These are usually part of a communication system from the extracellular to the intracellular environments. 

Since aminoglycoside complexes with membrane phosphoinositides are extremely stable, they could well exist in an intracellular environment with concentrations of aminoglycosides that are achieved in chemotherapeutic treatment. 

Modification of Cells for Transport Experiments Experimental control of intracellular environment, 171, 817 implantation of isolated carriers and receptors into living cells by Sendai virus envelope-mediated fusion, 171, 829 resonance energy transfer microscopy visual colocalization of fluorescent lipid probes in liposomes, 171, 850. 

A major class of insoluble proteins are recombinant proteins expressed (usually in Escherichia coli) as inclusion bodies. These are dense aggregates found inside cells that consist mainly of a desired recombinant product, but in a nonnative state. Inclusion bodies may form for a variety of reasons, such as insolubility of the product at the concentrations being produced, inability to fold correctly in the bacterial environment, or inability to form correct, or any, disulfide bonds in the reducing intracellular environment. Their purification is simple, since the inclusion bodies can be separated by differential centrifugation from other cellular constituents, giving almost pure product the problem is that the protein is not in a native state, and is insoluble. Some methods for obtaining an active product from inclusion bodies are described in Coligan et al. (2001). 

The underlying principle in regulation is maintaining a favorable intracellular environment in the most economical manner. The cell makes products in the amounts that are needed. Each pathway is regulated in a somewhat different way, ensuring that biochemical energy and substrates are efficiently utilized. 

Hundreds of biochemical reactions take place even in the cells of relatively simple microorganisms. Living systems have evolved a sophisticated hierarchy of controls that permits them to maintain a stable intracellular environment. These controls ensure that substances required for maintenance and growth are produced in amounts that are adequate without being excessive. Biochemical controls have developed in such a way that the cell can make adjustments in response to a changing external environment. Adjustments are needed because the temperature, ionic strength, acid concentration, and concentration of nutrients present in the... 

It is reasonable to conclude that achieving effective ribozyme-substrate interactions and ribozyme function in an intracellular environment is not a straightforward task, and that new strategies for expression and localization of ribozymes in the intracellular mileu will be required to permit the general utility of ribozymes as therapeutic agents. 

---