Nematode muscle nicotinic acetylcholine receptor (nAChR)

The nematode muscle nicotinic acetylcholine receptor (nAChR) is a pentameric ligand-gated ion channel essential for excitatory neurotransmission at the nematode neuromuscular junction (Martin et al., 2012, PubMed). It is a primary target for anthelmintic drugs, which often exploit the receptor's open channel state to induce paralysis in parasitic worms. Agonists like levamisole and pyrantel bind to the receptor, causing the channel to open and remain in a persistent active state, leading to depolarization block and spastic paralysis (Robertson et al., 2013, PubMed). Conversely, some antagonists or pore-blockers specifically target the open conformation to inhibit ion flow. This receptor is composed of various subunits, such as UNC-38 and UNC-29, which provide the structural basis for its cation selectivity (UniProt). Because these receptors differ significantly from mammalian subtypes, they offer a high degree of therapeutic selectivity for treating helminth infections (Wolstenholme, 2011, PubMed). Understanding the transition to the open channel state is crucial for developing new drugs that can overcome resistance in species like Haemonchus contortus.

Other names

Levamisole-sensitive nicotinic acetylcholine receptorL-type nAChRNematode neuromuscular junction acetylcholine receptorUNC-38/UNC-29/UNC-63 receptor complexNematode muscle nAChR

Agonist-induced persistent activation leading to spastic paralysis; Open-channel blockade; Competitive antagonism.