Advances in our understanding of nematode ion channels as potential anthelmintic targets

Int J Parasitol Drugs Drug Resist. 2022 Apr:18:52-86. doi: 10.1016/j.ijpddr.2021.12.001. Epub 2021 Dec 25.

Abstract

Ion channels are specialized multimeric proteins that underlie cell excitability. These channels integrate with a variety of neuromuscular and biological functions. In nematodes, the physiological behaviors including locomotion, navigation, feeding and reproduction, are regulated by these protein entities. Majority of the antinematodal chemotherapeutics target the ion channels to disrupt essential biological functions. Here, we have summarized current advances in our understanding of nematode ion channel pharmacology. We review cys-loop ligand gated ion channels (LGICs), including nicotinic acetylcholine receptors (nAChRs), acetylcholine-chloride gated ion channels (ACCs), glutamate-gated chloride channels (GluCls), and GABA (γ-aminobutyric acid) receptors, and other ionotropic receptors (transient receptor potential (TRP) channels and potassium ion channels). We have provided an update on the pharmacological properties of these channels from various nematodes. This article catalogs the differences in ion channel composition and resulting pharmacology in the phylum Nematoda. This diversity in ion channel subunit repertoire and pharmacology emphasizes the importance of pursuing species-specific drug target research. In this review, we have provided an overview of recent advances in techniques and functional assays available for screening ion channel properties and their application.

Keywords: GABA receptors; Glutamate-gated chloride channel; Ion channels; Nicotinic acetylcholine receptors; Patch clamp; TRP channels.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Anthelmintics* / metabolism
  • Anthelmintics* / pharmacology
  • Nematoda* / physiology
  • Receptors, GABA
  • Receptors, Nicotinic* / metabolism

Substances

  • Anthelmintics
  • Receptors, GABA
  • Receptors, Nicotinic
  • Acetylcholine