Abstract

Conotoxins are tools used by marine Conus snails to hunt and are a significant repository for marine drug research. Conotoxins highly selectively coordinate different subtypes of various ion channels, and a few have been used in pain management. Although more than 8000 conotoxin genes have been found, the biological activity and function of most have not yet been examined. In this report, we selected the toxin gene QcMNCL-XIII0.1 from our previous investigation and studied it in vitro. First, we successfully prepared active recombinant QcMNCL-XIII0.1 using a TrxA (Thioredoxin A)-assisted folding expression vector based on genetic engineering technology. Animal experiments showed that the recombinant QcMNCL-XIII0.1 exhibited nerve conduction inhibition similar to that of pethidine hydrochloride. With flow cytometry combined fluorescent probe Fluo-4 AM, we found that 10 ng/μL recombinant QcMNCL-XIII0.1 inhibited the fluorescence intensity by 31.07% in the 293T cell model transfected with Cav3.1, implying an interaction between α1G T-type calcium channel protein and recombinant QcMNCL-XIII0.1. This toxin could be an important drug in biomedical research and medicine for pain control.

Highlights

  • Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Abstract: Conotoxins are tools used by marine Conus snails to hunt and are a significant repository for marine drug research

  • QcMNCL-XIII0.1 may interact with the α1G T-type calcium channel protein, which suggests that it is a bioactive substance with important potential in analgesia and related fields

  • By the improved method of bullfrog sciatic nerve bioelectric activity, we defined its biological nerve-blocking activity, and by flow cytometry combined with fluorescent probe Fluo-4 AM, we preliminarily studied the function of QcMNCL-XIII0.1 in the 293T cell model

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Summary

Introduction

Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Abstract: Conotoxins are tools used by marine Conus snails to hunt and are a significant repository for marine drug research. Animal experiments showed that the recombinant QcMNCL-XIII0.1 exhibited nerve conduction inhibition similar to that of pethidine hydrochloride. With flow cytometry combined fluorescent probe Fluo-4 AM, we found that 10 ng/μL recombinant QcMNCL-XIII0.1 inhibited the fluorescence intensity by 31.07% in the 293T cell model transfected with Cav3.1, implying an interaction between α1G T-type calcium channel protein and recombinant QcMNCL-XIII0.1. This toxin could be an important drug in biomedical research and medicine for pain control. Key Contribution: We prepared a novel conotoxin QcMNCL-XIII0.1 from Conus quercinus, which exhibited nerve conduction inhibition similar to that of pethidine hydrochloride. QcMNCL-XIII0.1 may interact with the α1G T-type calcium channel protein, which suggests that it is a bioactive substance with important potential in analgesia and related fields

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