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neiliyerstiven neiliyerstiven
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7 years ago
The machanism of action of toxic effects through ion channels ? Undecided
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Educator
7 years ago
Any toxin? It depends heavily on this.

The flow of sodium ions into nerve cells is a necessary step in the conduction of nerve impulses in excitable nerve fibers and along axons. Normal axon cells have high concentrations of K+ ions and low concentrations of Na+ ions and have a negative potential. Stimulation of the axon results in an action potential which arises from a flow of Na+ ions into the cell and the generation of a positive membrane potential. Propagation of this depolarization along the nerve terminal presages all other events. The Na+ ions flow through the cellular membrane employing the sodium ion channel, a channel that is selective for sodium ions over potassium ions by an order of magnitude.

The channel itself is made up of a single peptide chain with four repeating units with each unit consisting of six trans-membrane helices. The trans-membrane pore is formed when the four units fold into a cluster with the center of the cluster the pore.

Tetrodotoxin is the poison that is produced by the puffer fish and a number of other animals. It is a virulent poison, the LD50 for the mouse is 10 nanograms. It acts by blocking the conduction of nerve impulses along nerve fibers and axons. The victim eventually dies from respiratory paralysis.

Tetrodotoxin is quite specific in blocking the Na+ ion channel and therefore the flow of Na+ ions while having no effect on K+ ions. Binding to the channel is relatively tight (Kd =10-10 nM). Whereas the hydrated sodium ion binds reversibly on a nanosecond time-scale, tetrodotoxin is bound for tens of seconds.



Tetrodotoxin, much larger than the sodium ion, acts like a cork in a bottle, preventing the flow of sodium until it slowly diffuses off. A mortal dose of tetrodotoxin is but a single milligram. Tetrodotoxin competes with the hydrated sodium cation and enters the Na+-channel where it binds. It is proposed that this binding results from the interaction of the positively charged guanidino group on the tetrodotoxin and negatively charged carboxylate groups on side chains in the mouth of the channel.
Source  1) http://www.life.umd.edu/grad/mlfsc/zctsim/ionchannel.html
2) http://bja.oxfordjournals.org/content/89/1/52.long
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