Transmembrane gates

Adenylyl Cyclases Guanylyl Cyclases Transmembrane Signalling Cyclic Adenosine Monophosphate Cyclic Guanosine Monophosphate Cyclic Nucleotide-gated Channels Phosphodiesterases... 

Extracellular ATP has been demonstrated to activate a depolarizing current in different neuronal and non-neuronal cell types. These receptors are also referred to as P2 receptors. The receptors can further be divided into the G-protein-coupled P2Y receptors and the ligand-gated ion channels P2X. Currently, seven P2X receptors (P2XJ-P2X- ) have been cloned (Table 3.3). The receptors exhibit between 26 and 50% overall amino-acid identities, with the highest level of conservation in the extracellular and transmembrane regions. P2X7 (also called P2Z) is the most distant member of the family. 

The receptors range in size from 379 to 595 amino acids. The receptors have two transmembrane regions with intracellular N- and C-termini (Figure 3.11). Extensive SCAM analysis suggests that TM2 forms the pore, and a conserved glycine residue in the middle of TM2 lines the narrowest part of the channel. The structure of the pore and the location of the gate have still not been... 

Many of these materials form voltage-gated transmembrane ion channels, i.e. they exhibit non-linear current voltage curves, unlike the polyene antibiotics and gramicidin A which have linear current voltage curves. Of the peptaibol antibiotics the most thoroughly investigated substance to date is alamethicin 201 203>. 

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). 

Ion channels, transporters and many receptors are polytopic. Polar and helix-destabilizing residues are likely to occur within their transmembrane segments to form the requisite gates, channels or binding domains. Transmembrane helices in polytopic proteins are usually... 

Structural models for voltage-dependent gating of ion channels must identify the voltage-sensors or gating charges (Fig. 6-5A) within the channel structure and suggest a plausible mechanism for transmembrane movement... 

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