Nicotinic acetylcholine receptors cation- selective

The open channel has in most cases a selective permeability, allowing a restricted class of ions to flow,for example Na+, K+, Ca++ or Cl- and, accordingly, these channels are called Na+-channels, K+-channels, Ca -channels and Cr-channels. In contrast, cation-permeable channels with little selectivity reject all anions but discriminate little among small cations. Little is known about the structures and functions of these non-selective cation channels [1], and so far only one of them, the nicotinic acetylcholine receptor (nAChR, see Nicotinic Receptors), has been characterized in depth [2, 3]. The nAChR is a ligand-gated channel (see below) that does not select well among cations the channel is even permeable to choline, glycine ethylester and tris buffer cations. A number of other plasma... 

Non-selective Cation Channels. Figure 1 The nicotinic acetylcholine receptor (nAChR) is localized within the cell membrane above the cell membrane is the synaptic cleft, below the cytoplasm. Drawing of the closed (left) and open (right) nAChR showing acetylcholine (ACh) binding and cation movement. Dimensions of the receptor were taken from references [2, 3]. 

Figure 6 shows the proposed subunit assembly structure of the nicotinic acetylcholine receptor channel." The inner wall of the lower half part is surrounded by hydroxyl side chains from Ser and Thr, and by carboxylates or amides from Asp, Glu, and Gin at the mouth. Furthermore, a Lys residue seems to offer ion pairing with the carboxylate at the mouth. Considering the possibly similar stabilizing effect of ether and hydroxyl groups to cations, the proposed artificial supramolecular channel could be regarded as a good model of the acetylcholine receptor channel, which selects cations over anions, but does not discriminate between alkali metals. 

The aqueous domains are large enough to permit rapid access of the ions to the membrane channel, but sufficiently constrained so that ion selectivity effects, as the result of charge interactions, are likely to be important. The nicotinic acetylcholine receptor channel is highly selective for cations. However, there is less specificity among the cations. The permeability sequence for monovalent cations, Cs > Rb > > Na" > Li suggests weak interactions... 

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). 

Nicotinic acetylcholine (ACh) receptors are responsible for transmission of nerve impulses from motor nerves to muscle fibers (muscle types) and for synaptic transmission in autonomic ganglia (neuronal types). They are also present in the brain, where they are presumed to be responsible for nicotine addiction, although little is known about their normal physiological function there. Nicotinic receptors form cation-selective ion channels. When a pulse of ACh is released at the nerve-muscle synapse, the channels in the postsynaptic membrane of the muscle cell open, and the initial electrochemical driving force is mainly for sodium ions to pass from the extracellular space into the interior of the cell. However, as the membrane depolarizes, the driving force increases for potassium ions to go in the opposite direction. Nicotinic channels (particularly some of the neuronal type) are also permeable to divalent cations, such as calcium. 

These characteristics are shared with subunits that form other ion channels/receptors and thus define a receptor superfamily, usually referred to as the nicotinic family. All members in this superfamily function as either cation- or anion-selective channels, thereby mediating fast excitatory or inhibitory synaptic transmission. In mammalian cells, the cation-selective members include nicotinic and 5HTg receptors, whereas the anion-selective members include GABA, GAB Ac, and glycine receptors. Anion-selective channels in this family are also found in invertebrates these channels are gated by glutamate, 5-HT, histidine, and acetylcholine (1). 

Upon cooperative interaction with an agonistic ligand, like acetylcholine or nicotine, at both a-subunits of the receptor, the cation-selective channel undergoes a conformational change that widens its pore to a diameter of 0.7 to 2.5-3 nm. This enables the cross-membrane flow of extracellular sodium or calcium ions into the cytosol of the cell. While homopentameric receptors have five binding sites, it is already sufficent to open the ion gate, as soon as two of them are occupied. 

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