Toxic Chemcial may be as lethal as it is helpful
In 2008, Chicago resident Edward Bachner was put on trial for attempting to kill his wife using tetrodotoxin (TTX), the poison ejected by a puffer fish. He placed multiple orders of the toxin to various biochemical companies, totaling about 162 milligrams of the poison. Bachner was caught before he could carry out his scheme. His plan initially seemed ill-thought-out; after all, there is a vast multitude of poisons that could have been easier to obtain.
Nevertheless, TTX is unique because of its currently incurable, quick-working effects on the nervous system. The chemical freezes muscular movement as the individual finally dies from respiration failure. However, an analysis of the drug at the neuronal level shows that small doses of this chemical could be medically advantageous.
Tetraethylammonium (TEA) is a similar chemical that may be analyzed with TTX because of the related routes that both the substances take in their method of destruction. The main difference is that TEA produces the somewhat opposite effects of TTX. Although the two do not counteract each other, both are toxic when consumed in great amounts, and both may be very helpful for the medical community in small doses.
Before considering TTX and TEA, we must look at the basic neuron action potential in order to understand how these specific toxins work.
A neuron begins at the resting potential; its membrane potential is -70 millivolts. (This potential refers to the electrical charge of the cell’s interior compared to its exterior surroundings.) During this resting potential period, a sodium-potassium pump pushes 3 Na+ ions out of the axonal membrane for every 2 K+ ions in, in order to maintain the electrical charge. The extracellular fluid has a preponderance of Cl– and Na+ ions and a minority of K+ and organic ions. On the other hand, the intracellular fluid has mostly K+ and organic ions and very little of the other two ions. When a neuron receives a type of neurotransmitter from the end of another neuron, the receiver neuron’s electrical charge increases. The neuron’s Na+ ion channels are manipulated to allow Na+ ions enter the neuron and thus increase the membrane potential. However, the firing rate must first pass a certain threshold in order to make the action potential. Upon reaching this action potential, the membrane potential undergoes depolarization, meaning it becomes more positive.
The neuronal charge either changes due to ionotropic receptors (where the ion channels are directly controlled to open or close according to the received neurotransmitter’s message) or metabotropic receptors (where the accepted neurotransmitter activates G proteins, which activate an enzyme that finally controls the ion channel). The main difference between the two receptors is that the metabotropic type follows more of an indirect process than that of the ionotropic type.
Once the ion channels are under control, the post ceding process is the same for both receptor types. Sodium’s ion channel is activated first. Sodium ions enter the neuron due to diffusion and electrostatic pressure. Because of the neuron’s negative nature, the positive Na+ ions are inclined to flow into the neuron. The electrical charge increases, meaning the neuron undergoes depolarization.
Upon reaching the height of the action potential, the K+ ion channels open. In response to this event, the Na+ channels close. The K+ ions now flow out of the membrane because of diffusion forces and the now extremely positive membrane potential that must be reduced. As these K+ ions flow out, they lower the neuron’s electrical charge. The membrane potential eventually becomes negative again. Hyperpolarization consequently occurs, where the electrical charge overshoots and becomes even lower than the resting potential of -70 mV. The K+ ion channel then closes, and the sodium-potassium pump rebalances the charge by transporting 3 Na+ ions back out for every 2 K+ ions back in again.
This entire process may occur within 3 milliseconds.
TTX is a neurotoxin that blocks the Na+ ion channel, thus preventing Na+ ions from entering the neuron after an action potential has been obtained. In the long run, TTX causes paralysis because movement is not possible. The change in electrical current ignites the neuron to aid in the process of muscular movement. However, this change in electrical current cannot travel through the neuronal axon because the neurotoxin blocks the Na+ ion channels that initiate this change in charge.
In the short run, a small dose of TTX could be given to help certain disorders or physical problems. Someone whose Na+ ion channels always overshoot and overrun longer than usual could benefit from a little TTX, which would shorten the duration of the Na+ ion transfer. Visibly, this person maybe may have extended uncontrollable movements or a disorder with the effects from Tourette’s Syndrome, but instead in which such uncontrollable twitches result from the Na+ ion channels overshooting. A small dose of TTX may reduce the uncontrollability of the movements because the action potential would be maintained to the more normal standard and duration. In a similar context, an individual in intense pain may be relieved as specific neurons’ functions are temporarily shut off. Shutting off the functions may help after chemotherapy or as an anesthetic, in which most to all of the sensory neurons must be “quieted” in order to relieve the total pain.
TEA functions similarly as it blocks the subsequent K+ ion channels in the action potential process. By doing so, the chemical prevents K+ ions from flowing out of the axon after depolarization. This chemical holds the neuron back from returning to its negative resting potential because the blockage prevents the positive K+ ions from leaving the changed positively charged cell. In the long run, if the K+ ion channels are blocked, the Na+ ion channels keep running Na+ ions into the neuron until the neuron becomes overly positive and dysfunctional. But in the short term, TEA could temporarily extend the depolarization period. In some disorder with effects like those in myasthenia gravis (where the individual has periodic sluggish movements), an individual may be sluggish because his neuronal action potentials are always weak. In such a scenario, the K+ ion channels may open early, causing the membrane potential to never reach its peak—around +40 mV. In this case, TEA could delay the K+ ion channel initiation, which would thus extend the flow period of Na+ ions through their channels. Extending the period in which the Na+ ion channels are open means positive ions would continue to come into the neuron. As a result, the membrane potential would reach its peak. This normal membrane potential peak means the neuron would successfully fire and carry the message through; therefore, the individual would not have sluggish movements.
In both the cases of TTX and TEA, the dosage is very important. Especially in the case of TTX, just a little extra dose could be fatal. For that reason, it may be a while before the general public can get a prescription medication of the chemical. (Bachner managed to sneak through the restrictive regulations in obtaining TTX using an alias as a marine researcher.) The chemical would also probably need to be modified so that it could be much weaker and potentially less harmful.)
TTX and TEA are two examples of substances that can be valuable in very small quantities but lethal in anything greater.
As usual, nature has proven that the smallest things are best.