I wanted to understand how the boulinum toxin interferes with synaptic transmission. How does it effect the transmission of the impulse from pre to post synaptic cell? Please try to explain from the perspective of synaptic transmission.
Individuals exposed to botulinum toxin develop progressive failure of neuromuscular transmission characterized by an abnormally small electrical response in muscle after maximal stimulation of the motor nerve, although activation and conduction in the motor nerve itself are normal. Repeated stimulation of the motor nerve leads to an increase in the amplitude of the muscle response. The initial step in toxin action involves the binding of the disulfide-linked, light chain—heavy chain complex to specific receptors on the presynaptic membrane. Molecules of toxin bound to the surface membrane are then internalized in membrane vesicles, which ultimately discharge their contents into lysosomes. The toxin must then cross the lysosomal membrane and enter the cytoplasm before it can interfere with transmitter release. Here, the amino-terminal portion of the heavy chain plays a unique role . It can form a transmembrane channel in a lipid bilayer that is large enough to allow an extended peptide chain to pass. In artificial bilayers, channel-forming activity is pH-dependent; it is most prominent when the side of the bilayer corresponding to the intralysosomal surface is at low pH, about 4.5, while the cytoplasmic face is neutral, pH 7.0, corresponding to the conditions that prevail in vivo.
Botox and Margarita's while smoking Virginia Slims!!
