From squid giant axon to automated patch-clamp: electrophysiology in venom and antivenom research

Shirin Ahmadi; Melisa Benard-Valle; Kim Boddum; Fernanda C Cardoso; Glenn F King; Andreas Hougaard Laustsen; Anne Ljungars

doi:10.3389/fphar.2023.1249336

From squid giant axon to automated patch-clamp: electrophysiology in venom and antivenom research

Front Pharmacol. 2023 Aug 24:14:1249336. doi: 10.3389/fphar.2023.1249336. eCollection 2023.

Authors

Shirin Ahmadi¹, Melisa Benard-Valle¹, Kim Boddum², Fernanda C Cardoso^{3

4}, Glenn F King^{3

4}, Andreas Hougaard Laustsen^#¹, Anne Ljungars¹

Affiliations

¹ Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
² Sophion Bioscience, Ballerup, Denmark.
³ Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia.
⁴ Australian Research Council Centre of Excellence for Innovations in Protein and Peptide Science, University of Queensland, St Lucia, QLD, Australia.

^# Contributed equally.

Abstract

Ion channels play a crucial role in diverse physiological processes, including neurotransmission and muscle contraction. Venomous creatures exploit the vital function of ion channels by producing toxins in their venoms that specifically target these ion channels to facilitate prey capture upon a bite or a sting. Envenoming can therefore lead to ion channel dysregulation, which for humans can result in severe medical complications that often necessitate interventions such as antivenom administration. Conversely, the discovery of highly potent and selective venom toxins with the capability of distinguishing between different isoforms and subtypes of ion channels has led to the development of beneficial therapeutics that are now in the clinic. This review encompasses the historical evolution of electrophysiology methodologies, highlighting their contributions to venom and antivenom research, including venom-based drug discovery and evaluation of antivenom efficacy. By discussing the applications and advancements in patch-clamp techniques, this review underscores the profound impact of electrophysiology in unravelling the intricate interplay between ion channels and venom toxins, ultimately leading to the development of drugs for envenoming and ion channel-related pathologies.

Keywords: antivenom; drug discovery; electrophysiology; ion channel; neurotoxin; patch-clamp; venom.

Publication types

Review

Grants and funding

AHL is supported by a grant from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program [850974], by a grant from the Villum Foundation [00025302], and a grant from the Wellcome Trust [221702/Z/20/Z]. GK is supported by a Principal Research Fellowship [APP1136889] from the Australian National Health and Medical Research Council and a Centre of Excellence Grant [CE200100012] from the Australian Research Council. FC is supported by a CDMRP from the U.S.A. Department of Defense [HT9425-23-1-0146] and an Ideas Grant from the Australian National Health and Medical Research Council [APP1188959]. MB-V is supported by a Eurotech postdoctoral fellow from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement [899987].