GABA-gated Cl- channel

Ascaris somatic muscle cells also possess inhibitory synaptic and extra-synaptic GABA-gated Cl channels (Martin, 1980). Activation of these... 

Ionotropic GABA receptors (GABA(A)-Rs and GABA(C)-Rs) are inhibitory (hyperpolarizing) GABA-gated Cl channels that have sequence homology with nACh-Rs... 

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). 

These events happen in a very rapid sequence. However, there is inertia in the system that maintains every impulse as a discrete event. When an impulse reaches the synapse, Ca++ channels open, vesicles with the transmitter substance fuse with the membrane, and the transmitter substance is released into the synaptic cleft. Transmitter substances act as keys for the gates on ion channels at the postsynaptic membrane. The transmitter substance from inhibitory synapses (e.g., GABA) opens Cl channels that suppress or stop the action of Na+ influx on the voltage difference, and the positive feedback this has on the Na+ 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. 

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. 

Ion channels (center). These receptors contain ligand-gated ion channels. Binding of the signaling substance opens the channels for ions such as Na, Ca, and Cl . This mechanism is mainly used by neurotransmitters such as acetylcholine (nicotinic receptor see p.224) and GABA (A receptor see p.354). 

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 demonstration of GABA receptors coupled to Cl channels in the posterior pituitary (Zhang and Jackson 1993) prevailed Zhang and Jackson (1995) by activation of these receptors and gating the Cl channels to alter membrane potential, action potentials, and the status of voltage-gated channels. Their results supported a depolarisation block mechanism in the inhibition of secretion by GABA. 

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