Glycine-gated Cl channels

The receptor-operated Cl -channels of the central nervous system (CNS) are gated by the respective agonists GABA and glycine. Most Cl -channels can be inhibited by disulphonate stilbenes. Muscle Cl -channels can be inhibited by anthracene-9-carboxylate (A9C) and probably by IAA-94. The ICOR Cl -channel is fairly sensitive to NPPB. It should be noted, however, that none of these probes, except for the GABA- and glycine-receptor Cl -channels, is of sufficient affinity and selectivity to permit the channel identification by its use. This dilemma is one of the reasons why the purification of epithelial Cl -channels lags behind that of the CNS Cl -channels. 

The amino acid glycine binds to pentameric glycine receptors (similar structure as nAChR) which are ligand-gated Cl- channels. Inhibitory glycinergic neurons are in the brain stem and spinal cord and regulate involuntary motoric via Renshaw interneurons. 

Ionotropic receptors (bottom left) are ligand-gated ion channels. When they open as a result of the transmitter s influence, ions flow in due to the membrane potential (see p. 126). If the inflowing ions are cations (Na"", C, Ca ""), depolarization of the membrane occurs and an action potential is triggered on the surface of the postsynaptic cell. This is the way in which stimulatory transmitters work (e.g., acetylcholine and glutamate). By contrast, if anions flow in (mainly Cl ), the result is hyperpolarization of the postsynaptic membrane, which makes the production of a postsynaptic action potential more dif cult. The action of inhibitory transmitters such as glycine and GABA is based on this effect. 

When comparing transmitter-gated ion channels on a functional level, one can discern between anion and cation channels. The former ones comprise the GABAa and glycine receptors, which display a rank order of anion selectivity of I- > Hr > Cl- and which are also permeable to HC()3. All other ionotropic receptors mentioned here are cation channels, which discriminate rather poorly between various monovalent cations, at least when compared with voltage-gated ion channels. Some... 

Glycine receptors (Gly-Rs) are inhibitory, strychnine-sensitive, Gly-gated chloride (Cl-) channels with homology to other NT-gated ion channel receptors such as the nACh-Rs. On Gly binding, the Gly-gated chloride (Cl-) channel opens with consequent inhibitory hyperpolarization (i.e. the transmembrane potential (t] m) becomes more negative inside with respect to the outside) (Table 3.3). 

Inhibitory glutamate receptors (iGlu-Rs) are inhibitory, Glu-gated ion channels related to the ionotropic GABA receptors and glycine receptors, the open channel being permeable to Cl- and sometimes to K+. The isoxazole alkaloid ibotenic acid activates iGlu-Rs (Table 3.3). 

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... 

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