VOODOO PHARMACOLOGY
Basic Neuronal Transmission or How These Animals Eat
Overview of Nervous System Organization
Neuron Structure
The central nervous system
The Human Brain
2.25 Lateral view of the exterior cerebral cortex
Neurotransmission
Neurotransmitter stimulatenext neuron
Neuronal Transmission
Neurons synapsewith other neurons
Wave of electrical current passesdown the axon
Current triggers release of neurotransmitter
Distribution of ions inside and outside a neuron
Membrane potential recording from a squid axon
Ion Channels Create Ion Gradients
Stages of the action potential
1. Sodium channel opens
2. Potassium channel opens
Wave of depolarization moves down the axon
Another animation: www.blackwellscience.com/matthews/
animate.html
Overview of Chemical Transmission
Synaptic transmission: simple version
Release of Neurotransmitter
Vesicular Release of Simple Neurotransmitters
Proteins and Vesicular Release
Vesicular Proteins involved in Release
Release of Peptide Neurotransmitters
Neurotransmitter inactivation
Terminal and somatodendritic autoreceptors
Postsynaptic Receptors
Postsynaptic Acetylcholine Receptor
Summation of local potentials
NaK
Receptor
Molecules are Targets not Anatomic Units
Channels
Vesicle proteinsMetabolizingenzymes
Na
K
Channels as Targets
• Sodium Channel– Block: stop action
potential– Prevent inactivation:
stimulation then failure
• Potassium Channel– Block: No
repolarization: repetitive activity
– Open: Neuron can’t be activated
Sodium Channel Toxins
• Block:– Tetrodotoxin (Puffer fish) Conotoxins (Cone mollusks)
• Activate/prevent inactivation– Saxitoxin- Dinoflagellates and Scorpion Toxins– Batrachotoxin: poison dart frogs
Potassium Channel Toxins
• Block– Apamin (Honey bee)– Dendrotoxin (Green mamba)– Charybdotoxin (Scorpion)
Conotoxins: multipurpose toxins
• Peptide neurotoxins– Calcium channels
specific for muscles
– Sodium channels
– Potassium channels
Poison Dart Frogs
• Toxins in skin discourage predation
• Toxins from food (ingested insects?)
• Combination of ion channel toxins– Batrachotoxins
Terminals
Terminals as Targets
• Activate release• Black widow spider• Inhibit release• Botulinum toxin
Botulinum Toxin: Medicine or Weapon of War?
• Bacterial toxin (Clostridium botulinum)
• Binds Ach terminal• Zinc proteases- there are
7 toxin isoforms (A-G)• Cleave proteins involved
in vesicle fusion with membrane– Synaptobrevin– SNAP25– syntaxin
• Prevents neurotransmitter release
Bo-Tox (Botulinum Toxin A
• Injected locally: paralyzes neuromuscular junction
• Use originally for facial spasm
• Used widely in cosmetic surgery
• Is it a viable weapon?????
Latrotoxin (Black Widow Spider Venom)
Calcium
Binds Neurexin: triggers vesicle fusion
Neurexin
LatrophilinCalcium
Receptors as Targets
• Antagonists: prevent receptor activation
• Agonists: stimulate then inactivate
• Acetylcholinesterase inhibitors: prevent degradation
Receptor
Acetylcholine Receptor Toxins
• Antagonists• Cobra toxins• Alpha bungarotoxin (Krait)• Alpha neurotoxin (mamba)• Agonists• Nicotine• ACH inhibitors• Mamba toxins: fasiculins
Na
K
Summary of Toxin Sites
Tetrodotoxin
Dendrotoxin
Latrotoxin (increases)
Botulinum (blocks)BungarotoxinAlpha neurotoxin
Mechanisms by which drugs can alter synaptic transmission
Voodoo Pharmacology: Zombi
• Give tetrodoxin: paralyze and decrease oxygen requirement
• Bury until limited brain damage has occurred
• Dig up and he is yours to control