GABAA-receptor channel

Neurosteroids prolong the mean open time of recombinant GABAa receptor channels. Whereas, at least in recombinant systems, the identity of the a and (3 subunits has little or no effect on neurosteroid action, substitution of the y subunit by a 8 subunit suppresses the GABA-modulatory activity of the neurosteroids. 

Kaila, K (1994) Ionic basis of GABAa receptor channel function in the nervous system. Prog. Neurobiol. 42 489-537. 

Very few of the CP-channels described above have been purified, and the amino acid sequence is only known for the GABAA-receptor channel, the glycine-receptor channel and the Torpedo CP-channel [3-5], a CP-channel from skeletal muscle [125] and a CP-channel from MDCK cells [128]. In the following the current status will be briefly summarized. 

The DNA for the GABAA-receptor channel has been translated to the respective RNA by in vitro transcription of the cDNAs (for a and P) inserted into plasmids. The two RNAs, when injected together into Xenopus oocytes, produced GABA-sensitive CP-currents [3]. 

Valium target. y-Aminobutyric acid (GABA) opens channels that are specific for chloride ions. The GABAa receptor channel is pharmacologically important because it Is the target of Valium, which is used to diminish anxietv. 

HT3 receptors belong to the ligand-gated ion channel receptor superfamily, similar to the nicotinic acetylcholine or GABAa receptors and share elec-trophysiological and structural patterns. The receptors... 

The GABAA-receptor and the glycine receptor are Cl-channels (Table 1). When they open at a resting membrane potential of about -60 mV, the consequence is an entry of Cl-, hyperpolarization and an inhibitory postsynaptic potential (DPSP Fig. 1). 

Figure 11.7 Presumed arrangement of GABAa receptor subunits to form a receptor-channel complex, (a) Diagrammatic representation of an individual subunit with four transmembrane regions, extracellular sites for glycosylation and a site for phosphorylation on the intracellular loop between M3 and M4. (b) Association of five subunits to form a central ionophore bounded by the M2 region of each subunit. The suggested stoichiometry of the most widely expressed form of receptor is 2a, 2 and ly. Shown below are the possible subunit combinations of one such benzodiazepine-sensitive receptor together with a benzodiazepine-insensitive receptor in which the 7 subunit is replaced by a c5, and a ti-containing receptor with four different subunit types...

Experimentally all GABA antagonists induce convulsions. These include the genuine receptor antagonist bicuculline, which competes with GABA for its recognition site on the GABAa receptor and picrotoxin, which binds to a different site more closely related to the chloride ion channel. 

As outlined above (see also Chapter 9), these drugs have been found to influence the Cl channel of the GABAa receptor. Phenobarbitone acts directly to prolong its... 

The last few years has seen an explosion in AEDs. Some of those mentioned above may fall by the wayside and others appear. At the time of writing, we could include felbamate, zonisamide oxcarbazepine and topiramate. They all appear to have a phenytoin-like action on sodium channels, although topiramate appears to also potentiate the action of GABA on GABAa receptors like the benzodiazepines but through a different site. 

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