Glutamate-gated chloride channels

Cully, D.F., Vassilatis, D.K., Liu, K.K., Paress, P.S., Vanderploeg, L.H.T. and Schaeffer, J.M. (1994) Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371, 707-711. 

Martin, R.J. (1995) An electrophysiological preparation of Ascaris suum pharyngeal muscle reveals a glutamate-gated chloride channel sensitive to the avermectin analogue milbemycin D. Parasitology 112, 252. 

Blocks transmission of nerve signals by interactions with glutamate-gated chloride channels Depolarization and spastic paralysis... 

Ivermectin binds selectively and with high affinity to glutamate gated chloride ion channels in invertebrate nerve and muscle cells. This leads to an increase in the permeability of cell membrane to chloride ions with hyperpolarization of nerve of muscle cell, resulting in paralysis and death of the parasite. 

Fairman, W.A. et al., (1995). A glutamate transporter which also has properties of a gated chloride channel. Nature 375, 599-603. 

There is little doubt that milbemycins and avermectins act on chloride channels associated with GABA receptors and amplify GABA functions in the mammalian central nervous system. In the free-living nematode, C elegans, however, avermectin was found to interact with glutamate-gated... 

Niemeyer MI et al (2003) A conserved pore-lining glutamate as a voltage- and chloride-dependent gate in the C1C-2 chloride channel. J Physiol 553 873-879... 

The insect GABA receptor-chloride ionophore complex is found in the CNS and also at peripheral neuromuscular sites. GABA receptors belong to a superfamily of ligand-gated ion channels known as Cys-loop receptors that include nicotinic acetylcholine receptors and glutamate-gated chloride channels (Lester, 2004). Cys-loop receptors are so named because... 

Etter A, Cully DF, Liu KK, Reiss B, Vassilatis DK, Schaeffer JM, Arena JP (1999) Picrotoxin Blockade of Invertebrate Glutamate Gated Chloride Channels Subunit Dependence and Evidence for Binding within the Pore. J Neurochem 72 318 Cleland TA (1996) Inhibitory Glutamate Receptor Channels. Mol Neurobiol 13 97 Yarowsky J, Carpenter DO (1978) A Comparison of Similar Ionic Responses to y-Amino-butyric Acid and Acetylcholine. J Neurophysiol 41 531... 

There are five macrocyclic lactones utilized in veterinary practice of which ivermectin (an aver-mectin) and moxidectin (a milbemycin) are approved for use in the horse. Ivermectin and moxidectin selectively paralyze parasites by increasing muscle chloride permeability through interaction with glutamate-gated chloride ion channels (McKellar Benchaoui 1996). There is evidence that ivermectin and moxidectin may have several sites of action within the parasite and the effects of these compounds may also differ between the nematode species (McKellar Benchaoui 1996, Martin 1997). 

Selamectin binds to glutamate gated chloride channels in the parasite s nervous system, causing them to remain open. This causes chloride ions to continuously flow into the nerve cell, changing the charge of the cell membrane. The continuous flow of chloride ions blocks neurotransmission, and transmission of stimuli to muscles is prevented. Selemectin has no such effect in the mammalian nervous system, and therefore, it is much safer than common insecticides. 

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