Ion channels functions

The actions of toxins may be classified according to the our current perspective of ion channel function. Channels open, or gate , in response to a range of stimuli , variables that perturb the population distribution among a set of possible channel... 

Hille, B (1994) Modulation of ion channel function by G protein-coupled receptors. Trends Neurosci. 17 531-536. 

Ion channels are macromolecular complexes that form aqueous pores in the lipid membrane. We have learned much about ion channel function from voltage clamp and patch clamp studies on channels still imbedded in native cell membranes [1-6, 8]. A diversity of channel types was discovered in the different cells in the body, where the repertoire of functioning channels is adapted to the special roles each cell plays [5]. The principal voltage-gated ones are the Na+, K+ and Ca2+ channels, and most of these are opened by membrane depolarizations. Figure 6-5A summarizes the major functional properties of a voltage-gated... 

AA metabolites and PAF have initially been studied in terms of their roles in the inflammatory response, such as increased vascular permeability and the activation of and infiltration by inflammatory cells. It is now becoming apparent, however, that these bioactive lipids have significant neurobiological actions in ion channel functions, receptors, neurotransmitter release, synaptic plasticity and neuronal gene expression. 

Ion transport in very dilute freshwater environments can also be problematic from the perspective of electrochemical theory. For example, electrochemical theory predicts that Na+ entry through epithelial channels will stop when the external Na+ is <0.1 mmol Na+ (typical of many freshwaters), given intracellular Na+ concentrations of 10-20 mmol 1 1 in gill epithelial cells [83], Thus elevation of Na+ concentrations at the epithelial surface (adsorption) becomes critical to ion-channel function and Na+ uptake into the cells [50], Alternatively, we might postulate other transporters coupled to the Na+ channel to drive uptake (e.g. H+ slippage [84] on the H+-ATPase). 

The variety of possible responses is further increased by the fact that receptor-coupled G proteins can either activate enzymes other than adenylate cyclase or can directly influence ion channel functions. 

A cumulative success of artificial ion-channel functions by simple molecules may disclose a wide gate for the design of ion channels and possible applications to ionics devices. Incorporation of these channels into bilayer lipid membrane systems may trigger the developments towards ionics devices. The conventional BLM system, however, is not very stable, one major drawback for the practical applications, and some stabilization methods, such as impregnating the material in micro-porous polycarbonate or polyester filters, are required. On the other hand,... 

Fig. 5.2. Structural principles of transmembrane receptors, a) Representation of the most important functional domains of transmembrane receptors, b) Examples of subunit structures. Transmembrane receptors can exist in a monomeric form (1), dimeric form (2) and as higher oligomers (3,4). Further subunits may associate at the extracellular and cytosohc domains, via disulfide bridges (3) or via non-covalent interactions (4). c) Examples of structures of the transmembrane domains of receptors. The transmembrane domain may be composed of an a-hehx (1) or several a-helices linked by loops at the cytosolic and extracellular side (2). The 7-helix transmembrane receptors are a frequently occurring receptor type (see 5.3). Several subunits of a transmembrane protein may associate into an ohgomeric structure (3), as is the case for voltage-controUed ion channels (e.g., K channel) or for receptors with intrinsic ion channel function (see Chapter 17).

Neurotransmitter-controlled Receptors with Intrinsic Ion Channel Function... 

At least two classes of neurotransmitter-controlled receptors with intrinsic ion channel function can be differentiated. One class includes receptors with the specific ligands acetylcholine, y-aminobutyric acid (GABA), glycine and serotonin. 

The genus Conus comprises approximately five hundred species of predatory cone snails and is therefore, one of the largest, if not the largest, single genus of marine animals alive. Each species of snail produces a unique venom with between 50 and 200 components. These sulfur-rich peptides or conotoxins are neuropharmacologically active and modulate ion channel function [235]. Any attempt to deal with these toxins within this review would not be feasible and the reader is referred to other excellent reviews on the subject [235,236]. 

Recent evidence also suggests that the distribution of phospholipids and proteins within the cell membrane is not random, but that certain areas of the cell membrane are organized into special regions or domains. 35,52 63 In particular, certain domains appear to consist primarily of lipids such as cholesterol and sphingolipids.27,50 These lipid domains are often described as lipid rafts that move freely about the cell membrane and these lipid rafts appear to be important in controlling various cell functions including cell signaling, endocytosis, and ion channel function.27,50 Future research will help further define the role of the lipid rafts and other specific domains within the cell membrane. 

Heidelberger R, Heinemann C, Neher E, Matthews G (1994) Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature 371 513-15 Henningfleld JE (1995) Nicotine medications for smoking cessation. N Engl J Med 333 1196-1203 Hille B (1994) Modulation of ion-channel function by G-protein-coupled receptors. Trends Neu-rosci 17 531-6... 

Yevenes GE, Peoples RW, Tapia JC, Parodi J, Soto X, Olate J, Aguayo LG (2003) Modulation of glycine-activated ion channel function by G-protein betagamma subunits. Nat Neurosci 6 819-24... 

The first step in viral replication and infection (Fig. 17.2) [31] is the interaction between the viral surface HA and sialic acid-containing glycoconjugates on the surface of respiratory tract cells. After binding, the virus is endocytosed, and the low pH of the endosome triggers HA-dependent fusion. The M2 ion channel functions to... 

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