Related Experiment Video
Updated: Mar 18, 2026
10:30
A High-throughput-compatible FRET-based Platform for Identification and Characterization of Botulinum Neurotoxin Light Chain Modulators
Published on: December 27, 2013
5.8K
Tick holocyclotoxins trigger host paralysis by presynaptic inhibition
Kirat K Chand1, Kah Meng Lee1, Nickolas A Lavidis1
1School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
Scientific Reports
|July 9, 2016
Summary
Australian paralysis ticks (Ixodes holocyclus) inject holocyclotoxins that cause paralysis by blocking calcium-dependent neurotransmitter release at the neuromuscular junction, offering new insights into tick neurotoxin mechanisms.
Area of Science:
- Neuroscience
- Toxicology
- Entomology
Background:
- Ticks are significant vectors of diseases and toxins.
- The Australian paralysis tick (Ixodes holocyclus) causes severe neurotoxicosis via holocyclotoxins (HTs).
- The precise mechanism of holocyclotoxin-induced paralysis remains uncharacterized.
Purpose of the Study:
- To investigate the molecular mechanism of holocyclotoxin (HT) action.
- To identify the specific target and pathway of HT-induced paralysis.
Main Methods:
- Purified holocyclotoxins (HT-1, HT-3, HT-12) from Ixodes holocyclus were used.
- The effect of toxins on neuromuscular transmission was analyzed.
- Dependence of transmitter release on extracellular calcium was assessed.
Main Results:
- Three holocyclotoxins (HT-1, HT-3, HT-12) were found to induce muscle paralysis.
- These toxins inhibit transmitter release by disrupting its dependence on extracellular calcium.
- This is the first study to use pure toxins, unlike previous work with salivary gland extracts.
Conclusions:
- Holocyclotoxins act by interfering with calcium-dependent neurotransmitter release.
- This provides a detailed understanding of the neurotoxic mechanism of Ixodes holocyclus.
- Findings advance knowledge of tick-borne neurotoxins and paralysis.
More Related Videos
Related Concept Videos
01:28Depolarizing Blockers: Mechanism of Action
3.3K
Depolarizing blockers act on skeletal muscle fibers' membranes and induce their depolarization. Most depolarizing blockers have two quaternary N+ atoms that bind the nicotinic acetylcholine receptors and cause neuromuscular blockade within minutes.
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
Succinylcholine is the most commonly used depolarizing blocker. Chemically, it constitutes two molecules of acetylcholine joined together by an acetate methyl group. They act on the receptors in the same way as acetylcholine. Because...
3.3K
01:17Nondepolarizing (Competitive) Neuromuscular Blockers: Mechanism of Action
3.4K
Nondepolarizing neuromuscular blockers induce paralysis by competitively blocking nicotinic acetylcholine receptors at the muscle end plate. Examples include pancuronium, mivacurium, vecuronium, and rocuronium. These quaternary ammonium derivatives are administered intravenously, are poorly absorbed, and are excreted via the kidneys.
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
Competitive antagonists prevent acetylcholine from binding to its receptor, inhibiting membrane depolarization. Without conformational changes or intrinsic...
3.4K
01:26Directly Acting Muscle Relaxants: Dantrolene and Botulinum Toxin
1.3K
Directly acting muscle relaxants like dantrolene and botulinum toxin (BoNT) have distinct mechanisms and applications. Dantrolene, a hydantoin derivative, acts on the ryanodine receptor (RYR1) in skeletal muscle cells. RYR1 are calcium channels present at the sarcoplasmic reticulum membrane. In response to excitation, they release calcium ions from the sarcoplasmic reticulum to the cytosol. Calcium promotes actin-myosin-mediated contraction of muscles.
The binding of dantrolene to the RYR1...
The binding of dantrolene to the RYR1...
1.3K
01:19Depolarizing Blockers: Pharmocokinetics
695
Depolarizing blockers are administered through intravenous injection. Succinylcholine is the most common choice of depolarizing blockers in emergency clinical practices. Although they have a rapid onset, they readily diffuse away from the motor end plate into the extracellular fluid. They are metabolized by enzymes such as liver butyrylcholinesterase and plasma pseudocholinesterases. This produces a short duration of action, typically 5-10 minutes long, unlike nondepolarizing blockers, which...
695
01:26Anticholinesterase Agents: Poisoning and Treatment
1.9K
Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
1.9K
01:29Neuromuscular Junction And Blockade
5.7K
The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
5.7K