Question

Toxins such as tetrodotoxin (from puffer fish and newts) and saxitoxin (from red-tide dinoflagellates) block voltage-gated \(\mathrm{Na}^{+}\) channels selectively. What effect would they have on currents in a voltage clamp to \(0 \mathrm{mV}\) ? How do you suppose they evolved?

Short answer

Toxins like tetrodotoxin and saxitoxin block voltage-gated Na+ channels. Thus, the current at 0mV would be significantly decreased or eliminated as these channels are blocked, preventing the generation of an action potential. They could have evolved as a defense mechanism to fend off potential predators, making these organisms dangerous to eat.

Step-by-step solution

Understanding the effect on currents in a voltage clamp

In the presence of toxins like tetrodotoxin and saxitoxin, voltage-gated Na+ channels would be blocked. This blockage doesn't allow Na+ ions to pass through the neuron membrane, even if the potentials are changed in a voltage clamp. Therefore, at 0 mV, these toxins would dramatically reduce or completely block any Na+ current. The effect is an absence of an action potential, leading to paralysis in extreme cases, as seen with pufferfish poisonings.

Explanation of the evolved toxins

Toxins could have evolved as a defense mechanism for the organism, preventing predators from eating them. For example, puffer fish have tetrodotoxin in their skin and other tissues, which can cause paralysis if ingested by predators, providing an effective deterrent. Similarly, red-tide dinoflagellates produce saxitoxin, leading to hazardous conditions for marine life and humans. The toxins could have evolved due to selective pressure from the environment.

Key concepts

Tetrodotoxin

Tetrodotoxin is a potent neurotoxin found primarily in pufferfish and some other marine animals. This toxin is notorious for blocking voltage-gated sodium (Na+) channels in nerve cells. When these channels are blocked, sodium ions cannot pass through and initiate an action potential.
This blockage leads to a decrease in nerve impulses and can cause numbness or paralysis in severe cases. Even when exposed to potentials via a voltage clamp, tetrodotoxin effectively prevents changes in current due to its binding affinity. It is strong enough that even at 0 mV, significant impairment or complete absence of Na+ current occurs.

• Origin: Mainly found in pufferfish and newts.
• Effect: Blocks Na+ channels, inhibiting nerve signal transmission.
• Outcome: Can cause paralysis and is highly toxic to predators and humans.

Always handle with care as it is lethal in minimal amounts.

Saxitoxin

Saxitoxin is another highly toxic compound primarily produced by marine dinoflagellates. These microorganisms are often responsible for harmful algal blooms, commonly known as "red tides." Like tetrodotoxin, saxitoxin blocks voltage-gated Na+ channels, thereby preventing sodium ions from entering nerve cells to propagate action potentials.
The blockage of sodium channels stops nerve conduction, which can result in paralytic shellfish poisoning in humans who consume contaminated seafood.

• Producer: Red-tide dinoflagellates.
• Molecular Target: Voltage-gated Na+ channels.
• Health Impact: Paralytic shellfish poisoning and potentially lethal effects in humans.

Saxitoxin is persistent in the environment, highlighting the need for careful monitoring of seafood sources.

Voltage-Gated Na+ Channels

Voltage-gated sodium channels are essential proteins in nerve cells that facilitate the initiation and propagation of action potentials. These channels open in response to changes in cell membrane potential, allowing Na+ ions to enter the cell. This influx causes a rapid rise in potential, termed depolarization.
Once depolarization reaches a threshold, it results in an action potential, allowing nerves to transmit signals.

• Function: Open and close in response to voltage changes, crucial for nerve signal transmission.
• Action Potential: Initiates and propagates nerve signals.
• Blockage Effects: Toxins like tetrodotoxin and saxitoxin block these channels, leading to loss of nerve function and paralysis.

These channels are vital for normal nerve function and are a key target for neurotoxins.

Evolution of Toxins

The evolution of toxins like tetrodotoxin and saxitoxin is thought to be driven by natural selection. Organisms producing these toxins likely developed them as defense mechanisms against predation, ensuring their survival.
Pufferfish, for instance, use tetrodotoxin to deter predators due to its paralytic effects. Similarly, dinoflagellates produce saxitoxin, which can significantly impact predators and even dictate the ecosystem's dynamic during red tides.

• Natural Selection: Toxins evolved to protect against predation.
• Survival Advantage: Provides specific organisms with a competitive edge.
• Environmental Impact: Influences the balance of marine life and human activities.

The intricate relationship between toxin production and ecological interactions underlines the adaptive strategies of organisms in response to their environment.