Anion channel

Why harp on this multitude of channel subtypes One important consequence is that it is very difficult at present to be sure about the spectrum of channels that may actually be targeted by a given drug in vivo. Observation of even strong interaction with one channel t5q)e in an in vitro mod- 

Chapter 5. Drugs that act on sodium and potassium channels 

Drugs that act on cation channels are used in various clinical applications. With sodium channels, these are  

Potassium channels are drug targets in the following contexts  

Drugs acting on calcium channels have a similar range of applications  

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The PBRis distinct from the central BZ receptor although both can be present in the same tissues in differing ratios. PBRs are predominately localized on the outer mitochondrial membrane and are thus intracellular BZ recognition sites. The PBR is composed of three subunits an 18,000 mol wt subunit that binds isoquinoline carboxamide derivatives a 30,000 mol wt subunit that binds BZs and a 32,000 mol wt voltage-dependent anion channel subunit. The porphyrins may be endogenous ligands for the PBR. PBRs are involved in the control of cell proliferation and differentiation and steroidogenesis. 

Chloride channels are membrane proteins that allow for the passive flow of anions across biological membranes. As chloride is the most abundant anion under physiological conditions, these channels are often called chloride channels instead of anion channels, even though other anions (such as iodide or nitrate) may permeate better. As some CLC proteins function as CF-channels, whereas other perform CF/H+-exchangers are also mentioned here. 

Inhibitory glycine receptor Strychnine-sensitive glycine receptor Glycine-gated chloride channel Glycine-gated anion channel... 

Receptor-binding of glycine induces the opening of an intrinsic anion channel highly selective for chloride and bicarbonate [2 4-]. Depending on the low reversal... 

Several compounds that inhibit vesicular glutamate transport have been identified These include the dyes Evans Blue and Rose Bengal. In addition, the stilbene derivative 4,4 -diisothiocyanatostilbene-2,2 -disulfonic acid (DEDS), a compound commonly used as a specific inhibitor of anion channels, inhibits vesicular glutamate transport. Most known inhibitors have limited use as they are membrane impermeant, with the exception of Rose Bengal. 

Figure 7 Mixld for iron (Fe) deficiency induced changes in root physiology and rhizo-sphere chemistry associated with Fc acquisition in strategy I plants. (Modified froin Ref. 1.) A. Stimulation of proton extru.sion by enhanced activity of the plasnialemma ATPase —> Felll solubilization in the rhizospherc. B. Enhanced exudation of reductanls and chela-tors (carhoxylates. phenolics) mediated by diffusion or anion channels Pe solubilization by Fein complexation and Felll reduction. C. Enhanced activity of plasma membrane (PM)-bound Felll reductase further stimulated by rhizosphere acidificalion (A). Reduction of FolII chelates, liberation of Fell. D. Uptake of Fell by a PM-bound Fell transporter.

Table 5 Effect of Anion-Channel Antagonists (Anthracene-9-carboxylic acid, ethacrynic acid each 100 fiM) and of Brefeldin A (Exocytosis Inhibitor 45 fiM) on Release of Phytosiderophores from Roots of Fe-Deficient Barley and Mai/.e...

WS Marshall, JW Hanrahan. (1991). Anion channels in the apical membrane of mammalian corneal epithelium primary cultures. Invest Ophthalmol Vis Sci 32 1562-1568. 

Joseph-Iiauzun, E., Farges, R., Delmas, P., Ferrara, P. Loison, G. (1997). The Mr 18,000 subunit of the peripheral-type benzodiazepine receptor exhibits both benzodiazepine and isoquinoline carboxamide binding sites in the absence of the voltage-dependent anion channel or of the adenine nucleotide carrier. J. Biol. Chem. 272, 28102-6. 

Beth, A.H., Conturo, T.E., Venkataramu, S.D., and Staros, J.V. (1986) Dynamics and interactions of the anion channel in intact human erythrocytes An electron paramagnetic resonance spectroscopic study employing a new membrane-impermeant bifunctional spin-label. Biochemistry 25, 3824-3832. 

Several different changes in mitochondria occur during apoptosis. These include a change in membrane potential (usually depolarization), increased production of reactive oxygen species, potassium channel activation, calcium ion uptake, increased membrane permeability and release of cytochrome c and apoptosis inducing factor (AIF) [25]. Increased permeability of the mitochondrial membranes is a pivotal event in apoptosis and appears to result from the formation of pores in the membrane the proteins that form such permeability transition pores (PTP) may include a voltage-dependent anion channel (VDAC), the adenine nucleotide translocator, cyclophilin D, the peripheral benzodiazepine receptor, hexokinase and... 

Dick GM, Kong ID, Sanders KM (1999) Effects of anion channel antagonists in canine colonic myocytes comparative pharmacology of Cl" Ca2+ and K+ currents. Br J Pharmacol 127 1819-1831... 

Ryan, R. M. and Vandenberg, R. J. (2002) Distinct conformational states mediate the transport and anion channel properties of the glutamate transporter EAAT-1. J. Biol. Chem. 277, 13494 13500. 

There are several hypotheses for a specific mechanism by which ONOO- can control the open state of the PTPC. Briefly the PTPC is regulated by primary constituents of the pore, including the inner membrane adenine nucleotide translocase (ANT) and the outer membrane protein voltage-dependent anion channel (VDAC or porin). The VDAC-ANT complex can bind to signaling proteins that modulate permeability transition, such as pro-apoptotic Bax (which opens the pore) and anti-apoptotic Bcl-2... 

Controls for Membrane Impermeance. Some fluoro-chromes can enter protoplasts via probenecid-sensitive anion channels (19) and control experiments must establish membrane impermeance. Soak the tissues in the fluorochrome at the concentration used for up to 12 h, rinsing and examining the tissues for fluorescence at hourly intervals. Cell viability is assessed by rate of cytoplasmic streaming, or by chloroplast autofluorescence, which declines in dead cells. 

The methods of solute transfer across the serosal/basolateral membrane can include ion channels and antiporters similar to those described earlier. In the case of serosally located cation channels, these primarily work because the intracellular electrolyte concentration is high enough to overcome the electrical gradient (e.g. some K+ channels). For anion channels, the negative charge inside the cell compared with the blood will help drive (repel) anions from the cell (e.g. CL efflux on voltage-sensitive channels in the intestine [58]). In the case of antiporters, the operation is fundamentally the same as that used in the mucosal membrane, except that the driving force is derived from an ion... 

Our model of cytochrome c release during apoptosis is not an alternative mechanism to the Bid/Bax-regulated release of cytochrome c. The voltage-dependent anion channel (VDAC) is known to be converted to a cytochrome c-permeant conduit by Bax. Furthermore, Bax protein can... 

McEnery, M.W., Snowman, A.M., Trifiletti, R.R., and Snyder, S.H., 1992, Isolation ofthe mitochondrial benzodiazepine receptor association with the voltage-dependent anion channel and the adenine nucleotide carrier, Proc.Natl.Acad.Sci. U.S.A. 89 3170-3174. 

Crompton, M., Virji, S., and Ward, J. M., 1998, CyclophUin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeabihty transition poie. EurJ Biochem 258 729-735. 

Chromate may go into cells through the general anion channel, leading to rapid intracellular accumulation (10). (Adapted from Plaper et ah, 2002)... 

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