Natural Ion Channel Proteins

These peptides induce transmembrane ion transport at rates comparable to those of natural ion-channel proteins, such as gramicidin A, and show considerable promise as antibiotics. 

Alkali metal transport in biochemistry is a vital process in maintenance of cell membrane potentials of use, for example, in nerve signal transduction and is at the core of some of the early work on artificial ionophores that mimic natural ion carriers such as valinomycin. Ionophore mediated ion transport is much slower than transport through cation and anion ion channel proteins, however. 

The development of biophysical techniques to make possible measurements of single ion channels in membrane bilayers has been fundamental to the advances in the understanding of how natural ionophores, particularly ion channel proteins, operate at the molecular level. The two principal techniques are the planar lipid... 

Many fundamental biological processes appear to depend on unique properties of inner hydrophilic domains of the membrane proteins in which ions or water molecules diffuse along the directional pathways. In the membrane protein systems simple inner functional moieties (i.e. carbonyl, hydroxyl, amide, etc.) are pointing toward the protein core, surrounded by the outer scaffolding protein wall orienting the transport direction. Bilayer or nanotube artificial membranes were developed with the hope of mimicking the natural ion-channels, which can directly benefit the fields of separations, sensors or storage-delivery devices. 

We have synthesized highly selective template-synthesized abiotic nanotube membranes that can be used as model systems for mimicking natural ion and protein channels. These nanotubes have diameters of the same order (1-100 nm) as those found... 

The implementation of natural ion channel systems for biosensor construction will suffer from the complexity of the structural and regeneration requirements imposed by the biological matrix. In a practical context, a more promising immediate solution seems to be the development of biosensors having an ion channel activity without implementation of ion channel proteins from natural sources, i.e. artificial ion channels. This involves modulation of ion conductivity through lipid membranes by means of alteration of phase structure by a wide variety of different selective binding interactions with, e.g. enzymes, antibodies, lectins, and others. 

These methods are based on the use of light waves to probe the macromolecular nature of ion channels and are useful for obtaining structural information about ion channel proteins. Without enough valid structural information, all data gleaned from traditional protein chemistry techniques are simply... 

Natural ion channels are high-molecular-weight membrane-spanning proteins that are believed to act via multiple a-helical strands that cross the membrane repeatedly. While much about protein channels is still not understood, it is believed that several helices arrange into an ion-selective pore, with ion transport occurring... 

At a cellular level, the activation of mAChRs leads to a wide spectrum of biochemical and electrophysiological responses [1, 5]. The precise pattern of responses that can be observed does not only depend on the nature of the activated G proteins (receptor subtypes) but also on which specific components of different signaling cascades (e.g. effector enzymes or ion channels) are actually expressed in the studied cell type or tissue. The observed effects can be caused by direct interactions of the activated G protein(s) with effector enzymes or ion channels or may be mediated by second messengers (Ca2+, DP3, etc.) generated upon mAChR stimulation. 

The actions of proteins isolated from sea anemones, or other coelenterates, involve mechanisms different from those described for saponins. Thus, hemolysins from sea anemone R macrodactylus are capable of forming ion channels directly in membranes (98). The basic protein from S. helianthus also forms channels in black-lipid membranes. These channels are permeable to cations and show rectification (99). This ability of S. helianthus toxin III to form channels depends upon the nature of the host lipid membrane (100). Cytolysin S. helianthus binds to sphingomyelin and this substance may well serve as the binding site in cell membranes (101-106). 

G-protein activation has a cyclical nature. The a subunit can hydrolyze the GTP that is bound to it, thereby allowing the heterotrimer to reform. The lifetime of individual aGTP subunits will vary (cf. the lifetimes of open ion channels). 

All cell membranes contain transmembrane proteins that form ion channels. These ion channels are usually selectively permeable to particular ions. Some channels, such as GABA-gated ion channels, are permeable to Cl ions and are inhibitory in nature because they make the inside of the nerve or muscle cells more negative as the Cl ions enter. Some ion channels are permeable to the cations Na and K, and an example of this type is the nicotinic acetylcholine-gated channel. Nicotinic channels have an excitatory effect when they open because Na ions enter and K ions leave through these channels. The cell becomes more positive inside and depolarizes. If the cell is a muscle cell, calcium accumulates in the cytoplasm and it contracts. We have found that all over the surface of Ascaris muscle there are GABA receptors (Martin, 1980) as well as nicotinic acetylcholine channels (Martin, 1982 Robertson and Martin, 1993). 

Muscarinic receptor activation causes inhibition of adenylyl cyclase, stimulation of phospholipase C and regulation of ion channels. Many types of neuron and effector cell respond to muscarinic receptor stimulation. Despite the diversity of responses that ensue, the initial event that follows ligand binding to the muscarinic receptor is, in all cases, the interaction of the receptor with a G protein. Depending on the nature of the G protein and the available effectors, the receptor-G-protein interaction can initiate any of several early biochemical events. Common responses elicited by muscarinic receptor occupation are inhibition of adenylyl cyclase, stimulation of phos-phoinositide hydrolysis and regulation of potassium or other ion channels [47] (Fig. 11-10). The particular receptor subtypes eliciting those responses are discussed below. (See also Chs 20 and 21.)... 

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