Intracellular chloride

R. Krapf, C. A. Berry, and A. S. Verkman, Estimation of intracellular chloride activity in isolated perfused rabbit proximal convoluted tubules using a fluorescent indicator, Biophys. J. 53, 955-962 (1988). 

M. Jennerwein, P. A. Andrews, Effect of Intracellular Chloride on the Cellular Pharmacodynamics of CM-Diamminodich loroplatinuml II) , Drug Metab. Dispos. 1995, 23, 178 - 184. 

Ivermectin binds to chloride ion channels in parasitic nerve and muscle cells, thereby increasing membrane permeability to chloride. Increased intracellular chloride results in hyperpolarization of nerve and muscle tissues, which results in paralysis and death of the parasite. Ivermectin is well tolerated during shortterm use in mild-to-moderate infections. Administration in more severe infections may cause swollen or tender lymph glands, fever, skin rash, itching, and joint and muscle pain, but these reactions may be... 

Duffey, M.E., Tumheim, K., Frizzell, R.A., Schultz, S.G. (1978). Intracellular chloride activities in rabbit gallbladder Direct evidence for the role of the sodium-gradient in energizing uphill chloride transport. J. Membr. Biol. 42, 229-245. 

Jennerwein M, Andrews PA (1995) Effect of intracellular chloride on the cellular pharmacodynamics of cis-diamminedichloroplatinum(II). Drug Metab Dispos 23 178-184... 

Actually, a number of studies have reported intracellular chloride-ion concentrations, between 10 and 76 x 10-3 M for various cell types including ovarian carcinoma cells (23 x 10-3 m), much larger than 4 x 10-3 M [31]. 

Davis-Kaplan, S. R., Askwith, C. C., Bengtzen, A. C., Radisky, D., and Kaplan, J. (1998). Chloride is an allosteric effector of copper assembly for the yeast multicopper oxidase Fet3p An unexpected role for intracellular chloride channels. Proc. Natl. Acad. Sci. USA 95, 13641-13645. 

Phenobarbital is the most commonly used anticonvulsant in horses as it has effects at doses lower than those that produce sedahon. It potentiates the actions of gamma-aminobutyric acid (GABA), the inhibitory neurotransmitter in the CNS. Neuronal stabilization by GABA in postsynaptic neurons occurs from increased intracellular chloride conductance, which hyperpolarizes the membrane the overall result is an increase in the seizure threshold and a decrease in the electrical activity of the seizure focus. 

VI. Vaughn-Jones, R. D., Intracellular chloride activity of quiescent cardiac purkinje fibers. 

During extracellular ion substitutions osmotic pressure was controlled by altering the concentration of sucrose in the saline (jjf). Changes in intracellular chloride concentration were monitored with intracellular recording electrodes containing the chloride sensitive resin Corning 47715. 

Neverthless, some guiding Interpretations for further experimental work are necessary, even If these be, admittedly, simple minded. We will assume that upon Injection of the clsplatln into the extracellular fluid of an animal the high chloride concentration (on the order of 100 milliequivalents per liter) limits any aquation reaction, and the drug remains intact as It courses through the body. Additional reactions of clsplatln with molecules in the blood will have to be left to the pharmacokinetlclsts to sort out. There is evidence to suggest that the Intact drug passively permeates cell membranes (viz, no active carrier is necessary). Usually, the intracellular chloride concentration Is lower than the extracellular value. 

Less is known about halorhodopsin. Observations (Schobert and Lanyi, 1982) suggest that it is a light-activated ion pump that drives chloride inward into the cell. It may serve to regain intracellular chloride lost by membrane-potential-driven extrusion. 

This accounts for about 2/3 of the chloride content of proximal tubule cells. The discrepancy between the active electrometric [Cl ] of 18.7 mM and the total intracellular chloride of 32.1 mM may be accounted for by one of three possibilities. First, a non-uniform distribution of chloride within different intracellular compartments. The lateral intercellular space which may not be readily penetrated by inulin is a region of hypertonicity rich in chloride. Second, 1/3 of the intracellular chloride may be bound to proteins or other macromolecules or fibrous elements. Third, cells of distal tubules may have a higher intracellular chloride (Conway et dl,y 1946) than those of proximal tubules. 

Still the electrometrically determined intracellular [Cl ] of 18.7 mM is too high and too far from an equilibrium distribution to be consistent with passive transport in the three-compartment system. Thus intracellular chloride is at a higher electrochemical potential than either luminal or peritubular fluid chloride. This results in the passive efflux of intracellular Cl across the luminal and peritubular cell membranes. Since the tubule cell has greater [Cl ] than that expected from a simple passive distribution (5-7 mM) between intracellular and the two extracellular fluid compartments. Cl must be actively transported into the cell. 

The electrometric intracellular chloride measured 2/3 of the total Cl content. Chloride was not distributed in accordance with the Donnan relationship since E > E across both membranes. The latter is evidence for active transport of Cl across the luminal membrane either by means of an ionic Cl pump or a neutral NaCl pump. 

So far the only successful control we have done is to take five frog hearts, wash them with isotonic sucrose to get rid of most of the extracellular chloride, and then make a pooled homogenate of them. Chloride activity in the homogenate was then measured with a liquid ion exchanger chloride microelectrode and with a Ag-AgCl electrode. The measurements with the two electrodes agree to within 1 mM. In view of this, we feel that we are measuring the true intracellular chloride activity. 

Oyama Y, Walker JL, Eyzaguirre C. The intracellular chloride activity of glomus cells in the isolated rabbit carotid body. Brain Res 1986 368(1) 167-169. 

Zhang, L. L. Pathak, H. R. Coulter, D. A. Freed, M. A. Vardi, N. Shift of intracellular chloride concentration in ganglion and amacrine cells of developing mouse retina. J. Neurophysiol. 2006, 95, 2404-2416. 

Inglefleld, J. R. Schwartz-Bloom, R. D. Using confocal microscopy and the fluorescent indicator, 6-methoxy-A-ethylquinolinium iodide, to measure changes in intracellular chloride. Methods Enzymol. 1999, 307, 469 81. 

Pilas, B. Durack, G. A flow cytometric method for measurement of intracellular chloride concentration in lymphocytes using the halide-specific probe 6-methoxy-AT-(3-sulfopropyl) quinolinium (SPQ). Cytometry 1997, 28, 316-322. 

Garcia, L. Rigoulet, M. Georgescauld, D. Dufy, B. Sartor, P. Regulation of intracellular chloride concentration in rat lactotrophs possible role of mitochondria. FEBS Lett. 1997, 400, 113-118. 

Yarbrough, J. W. Merryman, J. I. Barnhill, M. A. Hahn, K. A. Inhibitors of intracellular chloride regulation induce cisplatin resistance in canine osteosarcoma cells. In Vivo 1999, 13, 375-384. 

Bolton, T. B., Vaughanjones, R. D., Continuous direct measurement of intracellular chloride and pH in frog skeletal-muscle. J Physiol Land 1977, 270(3), 801—833. 

As noted above, cw-DDP enters cells by diffusion where it is converted to an active form. This is due to the lower intracellular chloride concentration, which promotes ligand exchange of chloride for water and thus formation of the active aquated complex. Thus, the platinum-containing complex should be neutral to enter the cell and labile chloride groups need to be present to form the active species widiin the cell. The antineoplastic activity of cw-DDP appears to be related to its interaction with DNA nucleotides, as a monoaquo species. The monohydrated complex reacts with the DNA nucleotide, forming intra/interstrand crosslinks. Of the four nucleic acid bases, cw-DDP has been shown to preferentially associate with guanine. The most common are intrastrand crosslinks between adjacent guanines. ... 

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