Deorphanization of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning

Abstract

Deorphanization of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learningHighlights d Characterization of five new monoamine-gated ion channels in C. elegans d The serotonin-gated cation channel LGC-50 is required for aversive learning d Pathogen exposure redistributes LGC-50 to synaptic processes d Regulated trafficking of LGC-50 is critical for the learning mechanism

A Novel and Functionally Diverse Class of Acetylcholine-gated Ion Channels

“…Data was gathered over at least two occasions, using different batches of oocytes. Peak current for each dose was normalised to the oocyte maximum current using a custom-built python script (Morud et al, 2021). Normalised data was imported into Graphpad (Prism) and fitted to either a three or four parameter nonlinear Hill equation to obtain the highest degree of fit and calculate the EC 50 .…”

“…Ion selectivity was detected using a voltage ramp protocol from -80mV to +60mV (20mV/s) in the presence of the primary agonist in three different solutions: ND96, NMDG (Na + free) and Na Gluconate (low Cl - ) solutions. Data was normalised to max current and ΔE Rev was calculated using a custom-built python script (Morud et al, 2021). The resulting individual values or mean, SD and n for each construct was imported in GraphPad for further plotting and statistical analysis.…”

“…The agonist concentrations remained constant. Antagonist IC 50 values were calculated using a second custom-built python script (Morud et al, 2021). Normalised data was imported into Graphpad (Prism) and fitted to either a three or four parameter nonlinear Hill equation to obtain the highest degree of fit and calculate the IC 50 .…”

“…For example, insects and nematodes express inhibitory glutamate receptors from the Cys-loop superfamily, localised both in neurons and muscles, which are targets of the anthelminthic drug ivermectin (Cully et al, 1996, 1994). Many animals including insects, nematodes and mammals also express LGICs which can be gated by aminergic ligands, including histamine-gated chloride channels (Gisselmann et al, 2002), important for fly visual processing, a number of nematode channels, involved in learning and motor control (Morud et al, 2021; Pirri et al, 2009), as well as the excitatory mammalian 5-HT 3 receptor (Kondo et al, 2014; Lombaert et al, 2018). Even more divergent roles for LGICs have been identified in marine species, where LGICs gated by terpenes and chloroquine function as chemoreceptors in octopus (van Giesen et al, 2020).…”

PharmacoGenetic targeting of a C. elegans essential neuron provides an in vivo screening for novel modulators of nematode ion channel function

“…MOD-1 and related biogenic amine and amino acid receptors are an under investigated class of ligand gated ion channels (Morud et al, 2021). In the case of MOD-1 there is a clear indication that they encode a receptor subunit that is capable of forming a functional homoligomeric anion channel (Ranganathan et al, 2000).…”