Ion conductance channel

Urry, D. W., A molecular theory of ion-conducting channels A field dependent transition between conducting and non-conducting conformations, Proc. Natl. Acad. Sci. USA, 69, 1610 (1972). 

As has been mentioned previously, gramicidin has limited utility as an antibiotic because of its hemolytic activity (Section 1.0). Various workers have utilized the hemolytic property of the antibiotic as an assay tool. The hemolytic activity of gramicidin is probably due to its ability to form ion conducting channels in the membranes of red blood cells. The loss of isotonicity causes the cells to rupture. 

The AChR consists of five subunits surrounding an ion-conducting channel (Fig. 28.2). Activation of the binding sites on the two a-subunits results in a conformational change. This allows the simultaneous inflow of Na+ and Ca++ and outflow of K+, with a net inflow of positive charge. The response to a spontaneously secreted quantum of ACh (that is, activation of several thousand AChRs) is seen as a miniature EPC. With nerve stimulation, many quanta are released synchronously to produce a fuU-sized EPC, which is the sum-mated response of the 200 or so individual miniature EPCs. The EPC is a local graded current that in normal conditions triggers an action potential in the adjacent muscle membrane (Fig. 28.1). 

Since the number of ion-conducting channels is small, the rate of sodium passage through the open channels must be extremely rapid and has been estimated as -108 ions / s.433 This is within an order of magnitude of the diffusion-limited rate (Eq. 9-30). 

Abel, E. Maguire, G. E. M. Meadows, E. S. Murillo, O. Jin, T. Gokel, G. W., (1997) Planar bilayer conductance and fluorescent studies confirm the function and location of a synthetic sodium-ion-conducting channel in a phospholipid bilayer membrane J. Am. Chem. Soc. 119, 9061-9062. 

The ion-conducting channel itself is likely similar to the structurally characterized K+ channel (Section 13.5.6). At least three molecules of IP3 must bind to sites on the cytosolic side of the membrane protein to open the channel and release... 

The po.ssible existence of a junction between muscle and nerve was suggested as early as 1856, when Claude Bernard ob.servcd that the site of action of curare was neither the nerve nor the muscle. Since that lime, it has been agreed that ACh mediates transmission at the neuromuscular junction by a sequence of events described above in this chapter. The neuromuscular junction consists of the axon impinging onto a specialised area of the mu.scle known as the muscle end plate. The axon is covered with a myelin sheath, containing the nodes of Ranvier, but is bare at the ending. The nerve terminal is separated from the end plate by a gap of 200 A. The subsynaptic membrane of the end plate contains the cholincigic receptor, the ion-conducting channels (which are opened under the influence of ACh), and AChE. 

The first goal of this work is to develop a sound theoretical foundation for the description of ion transport along a channel. Once this description is established, it is possible to consider refinements interactions with channel wall vibrations and ion transfer across interfaces that control the flow of ions from solution, for example, into the channel. In this paper, I examine a model for ion transport in screened, but otherwise electrically neutral channels. Band states may exist for ions in such systems. There is evidence [10] that ion conduction channels do not need to have incorporated water to solvate mobile ions effectively aromatic pi-electrons are sufficiently polarizable to interact strongly with a simple cation to create an association that is as effective as water solvation. Thus, the models constructed assume only that the sources (molecules) that make up the channel walls... 

Ion conducting channels across the membrane are formed either by parallel or serial alignment of suitable organic molecules. The outside of a channel should be lipophilic, in order to allow for an energetically favourable interaction with the lipid chains of the membrane. Inside the channel, electrophilic groups should produce a polar cylindrical cavity through which partially or completely desolvated cations can permeate. 

The first question concerns the physical nature of such a channel in the F0 subunit. A useful model is provided by the work of Lear et al. (37, 38), who found that synthetic serine-leucine peptides form ion-conducting channels in planar lipid membranes. The channels apparently are produced when a-helical configurations of the peptides form clusters within the bilayer. For instance, when a 21 residue peptide H2N—(LSSLLSL)3—CONH2 was incorporated into a planar lipid bilayer membrane, channels appeared that had cation conducting properties that resembled those of the acetylcholine... 

Figure 12.10 presents a PEO-based azo LCBC film, which exhibits well-ordered hydrophilic PEO nanocylinders with hexagonal packing embedded in an azo LC matrix. The anisotropic PEO nanocylinders can be used as ion-conductive channels since PEO has been widely used as a solid electrolyte (Fig. 12.22). 

Mueller and Rudin and Lev and Buzhinsky found, however, that valinomycin induced an increase in the ion permeability of black lipid membranes which obviously were free of all complicated biological transducers. An alternative mechanism was proposed to explain the activity of valinomycin in which it was suggested that valinomycin forms an ion conducting channel across the lipid bilayer This mechanism was rejected in favor of the currently accepted mobile carrier mechanism when it was demonstrated that both valinomycin and nigericin could transport ions across bulk phases too thick to accommodate stacked molecular channels The generic term ionophore, i.e. ion carrier, was chosen to describe these compounds by Pressman et al. in order to emphasize the dynamic aspects of the transport mechanism Although this term is widely accepted, Ovchinnikov... 

The structure would be long enough to span the membrane, and the pore so formed woidd be lined with hydrophilic groups to provide an ion-conducting channel. 

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