How Botox Works
Basic Explanation of How Botox Works
BOTOX® (botulinum toxin type A) works by preventing the release of the neurotransmitter acetylcholine from vesicles at the neuromuscular junction. Put another way, Botox works by blocking the transmission of acetylcholine from the nerves to the muscle. Acetylcholine is a chemical neurotransmitter which sends a signal to the muscle telling the muscle to contract or tense up.
For example, when you move your hand to move your computer mouse or you move your eyes to read this sentence, your brain is sending a signal to your nerve cells to release acetylcholine to the muscle cells which in turn contract accordingly to produce the desired movement.
Now, if the flow of acetylcholine, from the nerve to the muscle, is blocked or significantly reduced, the muscle can no longer contract and it simply relaxes. This is how Botox works, by blocking the message to contract that acetylcholine mediates between the nerve cell and the muscle cell.
The final result of Botox injections for cosmetic purposes is that specific muscles of the face are “paralyzed” and therefore wrinkled areas smooth out and soften.
Botox injections are only useful for wrinkles caused by the contraction of facial muscles. These include most commonly the glabellar lines (also known as the “11” lines that form between the eyebrows), forehead wrinkles and crow’s feet.
Botox injections also works for many therapeutic medical purposes such as blepharospasm (uncontrolled eye blinking), strabismus (crossed-eyes), cervical dystonia (involuntary neck muscle spasms), migraine headaches, overactive bladder, excessive sweating, cerebral palsy, chronic lower back pain, etc.
Scientific Explanation of How Botox Works
The active ingredient of Botox is Botulinum Toxin Type A. There are seven different types (designated as A through G) of botulinum toxins produced by different strains of the Clostridium botulinum bacterium. All the various types of botulinum toxin inhibit acetylcholine release, although their intracellular target proteins, the characteristics of their actions, and their potencies vary substantially.
Botox is made up of a protein complex purified from the bacterium Clostridium botulinum. Botulinum Toxin Type A is a component of this purified protein complex.
As we saw in the Basic Explanation of How Botox Works, BOTOX® (botulinum toxin type A) works by preventing the release of the neurotransmitter acetylcholine from vesicles at the neuromuscular junction.
Now, let’s delve a little deeper into how Botox injections work to makes this blockage of acetylcholine happen.
First, in order to understand the detailed scientific explanation of how Botox works we will need to explore how the release of acetylcholine from the nerve ending occurs.
The junction where a nerve cell and a muscle cell meets is called a neuromuscular synapse. “Neuro-“ refers to nerves and “muscular” refers to muscles. It is at this synaptic level that Botox works.
Diagram of a Neuromuscular Synapse
Skeletal muscles are innervated by motoneurons that have their cell bodies in the brain stem or spinal cord. Motoneuron axons pass out of the central nervous system in the anterior spinal roots to form peripheral nerves that branch within the skeletal muscle into terminals and contact several striated muscle fibers, forming neuromuscular synapses. A group of striated muscle fibers innervated by a single motoneuron forms a motor unit. The signal to a muscle to contract originates in the central nervous system and travels as an action potential down the motoneuron to the skeletal muscle fibers. The action potential depolarizes the motoneuron terminal to stimulate the release of acetylcholine into the neuromuscular synaptic cleft via elevating the Ca 2+ concentration. Acetylcholine is released from the cytosol by Ca 2+-regulated exocytosis, a multi-stage process that involves the participation of several proteins collectively called SNAREs ( soluble N-ethylmaleimide–sensitive factor attachment protein receptors). When acetylcholine reaches the postsynaptic muscle membrane, its binding to nicotinic cholinergic receptors opens a transmembrane channel, resulting in an influx of sodium ions (Na +) into the muscle fiber and subsequent efflux of potassium (K +); this initial reduction in the membrane potential of the muscle fiber generates an endplate potential. When the endplate potential reaches a threshold, an action potential is created in the muscle, causing it to contract.
It is believed that Botox works via a multi-step mechanism of action. The steps by which Botox injections work are:
- binding of Botulinum Toxin Type A (Botox) to ecto-acceptors on the nerve ending
- acceptor-mediated internalization (the Botox molecule is taken into the nerve cell)
- translocation to the cytosol (cytosol is the internal fluid of the nerve cell)
- inhibition of Ca 2+-dependent neurotransmitter release.
Binding to the presynaptic acceptor requires the C-terminal half of the heavy chain (molecular weight = 100 kDa), which can be maintained in the correct confirmation by its association with the light chain (molecular weight = 50 kDa). The toxin is then internalized by receptor-mediated endocytosis until it is completely circumscribed in a vesicle. At that point, the active moiety passes through the vesicle wall and the protease of the light chain cleaves one of the proteins responsible for vesicle fusion and release of acetylcholine.
Acetylcholine in nerve terminals is packaged in vesicles. On nerve stimulation, which raised the intra-neuronal Ca 2+ concentrations, the vesicle membrane fuses with the plasmalemma of the nerve terminal, releasing the transmitter into the synaptic cleft. The process is mediated by a series of proteins collectively called the SNARE proteins. Botox, taken up into the nerve terminals, cleaves the SNARE proteins, preventing creation of the functional fusion complex and, thus, blocking the release of acetylcholine.
Diagram Showing How Botox Injections Work
