Invertebrate gamma-aminobutyric acid-gated chloride channel (GABA-Cl)

Invertebrate gamma-aminobutyric acid (GABA)-gated chloride channels are essential inhibitory neurotransmitter receptors found in the nervous system of arthropods, including Demodex mites (Demodex folliculorum and Demodex brevis). These channels belong to the Cys-loop superfamily of ligand-gated ion channels and mediate fast inhibitory synaptic transmission by allowing the influx of chloride ions upon GABA binding, which hyperpolarizes the postsynaptic neuron. In Demodex mites, these receptors are critical for regulating motor activity and coordination. Overgrowth of these mites is a primary factor in the pathogenesis of Demodex blepharitis and is associated with rosacea. Therapeutic agents such as lotilaner act as potent, non-competitive antagonists of these channels, specifically binding to the channel pore to block chloride ion flow. This blockade leads to uncontrolled nervous system hyperexcitation, resulting in spastic paralysis and the death of the mite. Because the molecular structure of these invertebrate channels differs significantly from mammalian GABA receptors, they serve as highly selective targets with a favorable safety profile for human use (FDA, 2023; Journal of Ocular Pharmacology and Therapeutics, 2023).

Other names

GABA receptorRDL receptorResistance to dieldrin proteinInvertebrate GABA-gated ion channelGABA-gated chloride channel

Non-competitive antagonism of the GABA-gated chloride channel, which prevents the influx of inhibitory chloride ions, leading to mite hyperexcitation, paralysis, and death.