GABA -gated

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). 

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

The GABA-gated chloride ion channel is modulated by several classes of drugs that bind to allosteric sites on the receptor complex the benzodiazepines, barbiturates and related intravenous general anesthetics such as etomidate and propofol, as well as anesthetic steroids and endogenous neurosteroids. It appears that some types of GABAa receptor are directly enhanced by ethanol and volatile general anesthetics (Fig. 16-2) [7,8,20]. 

Schwartz-Bloom RD, CookTA, Yu X. (1996). Inhibition of GABA-gated chloride channels in brain by the arachidonic acid metabolite, thromboxane A2. Neuropharmacology. 35(9-10) 1347-53. 

In the retina, homomeric receptors consisting of the p-subunit represent a particular class of GABA-gated chloride channels. Their GABA site is insensitive to bicuculline and baclofen and they are not modulated by barbiturates or benzodiazepines. Due to these distinctive features, the receptors are sometimes termed GABAc receptors (Bormann 2000), although they are be considered a homomeric class of GABAa receptors (Barnard et al. 1998). 

Barbiturates also facilitate the actions of GABA at multiple sites in the central nervous system, but—in contrast to benzodiazepines—they appear to increase the duration of the GABA-gated chloride channel openings. At high... 

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

Insecticides Interfering with GABA-Gated Chloride Channels... 

GABA-gated chloride channels Cyclodienes, lindane, phenylpyrazoles, Avermectins, emamectin benzoate, milbemectin Antagonism Chloride channel activators... 

The 1-phenylpyrazole core has been shown to bestow pharmacological activity in a number of areas in the pharmaceutical and agrochemical industries. In the latter field, select examples of biological activities include insecticidal, miticidal, and herbicidal. More specifically, 1-phenylpyrazoles with alkyl, acyl, thioalkyl, or cyano substituents at the 4-position exhibit potent insecticidal activity. In particular, 5-amino-I-(2,6-dichloro-4-trifluoro-methylphenyl)-4-trifluoromethanesulfinyl-l//-pyrazole-3-carbonitrile (Fipronil ) is one of the most commercially successful insecticides. In fleas, ticks, and other arthropods, it acts as a gamma-aminobutyric acid (GABA)-gated... 

It has now been well established that avermectins open a chloride ion channel in invertebrates which is distinct from GABA-gated chloride channels [190,191]. Turner and Schaeffer [192] have shown that ivermectin specifically increases mem-... 

---