Comparative Neuromuscular Blocking Actions of Presynaptic Phospholipase A₂ Neurotoxins in Chick Biventer Nerve-muscle Preparations

Document Type : Original Articles

Authors

1 Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.

2 Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.

3 Philipps University Marburg, Marburg, Germany.

10.32598/ARI.81.3.3990

Abstract

Introduction: Among the major toxic constituents of snake venoms, phospholipases A₂ (PLA₂) represent a highly diverse enzyme family responsible for a variety of pathological effects, including pronounced myotoxicity and neurotoxicity. 
Materials & Methods: This study focuses on presynaptically active PLA₂ neurotoxins, β-bungarotoxin (BuTx), taipoxin, crotoxin, notexin, and ammodytoxin C (Amtx). We examined and compared their neuromuscular blocking actions using indirectly stimulated chick biventer cervicis nerve-muscle preparations.
Results: BuTx was tested at three concentrations (47, 4.7, and 0.47 nM), producing time and concentration-dependent neuromuscular blockade. It abolished twitch responses within 60 minutes at 47 nM, 120 minutes at 4.7 nM, and 180 minutes at 0.47 nM. All other toxins tested also induced complete neuromuscular paralysis at the given concentrations. Our findings demonstrate that these neurotoxins impair neuromuscular transmission in a dose-dependent manner, ultimately resulting in irreversible muscle paralysis. Among them, BuTx displayed the highest potency, while Amtx was the least potent. To assess postsynaptic function, contracture responses to exogenous acetylcholine (ACh) (1 mM), carbachol (20 μM), and potassium chloride (40 mM) were recorded before and after toxin exposure in the absence of nerve stimulation. These responses remained unchanged, indicating that postsynaptic sensitivity was preserved.   
Conclusion: A deeper understanding of the mechanisms underlying venom-induced neurotoxicity may improve diagnostic accuracy and support the development of effective treatments for snakebite envenomation, reducing associated morbidity and mortality.

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