What's Killing West Coast Marine Mammals? And Why?

It’s becoming increasingly common to find seals washed up on Southern California beaches—the victims of a potent neurotoxin called domoic acid. And it’s not just seals; dolphins, whales, and seabirds are falling prey, too. But not fish. In fact, fish are at least indirectly part of the problem. More on that in a moment.

Why? It all comes down to glutamic acid receptors—something that’s far from intuitively obvious. I’ll try to make this discussion as non-neurotoxic as possible.

Glutamic acid receptors—including a subtype called kainate receptors belong to a class called ionotropic receptors. This is one of several ways the nervous system regulates ion movement—and, in turn, neurological function—in mammals and birds. These receptors fall into two broad categories, acting like molecular on-off switches for nerve signaling.

• Voltage-gated ion channels open or close in response to changes in the electrical charge across a cell’s membrane. This allows specific ions (like Na⁺, K⁺, or Ca²⁺) to flow in or out, creating the electrical signals that drive everything from thought to muscle movement. One well-known example is the voltage-gated sodium channel—the molecular spark behind every nerve impulse in your body.
• Ionotropic receptors, on the other hand, are ligand-gated ion channels. They open when a specific chemical—usually a neurotransmitter—binds to them. Glutamic acid receptors fall into this broad category. Specifically, the domoic acid screws up the machinery at the kainate receptor [1], one member of the glutamic acid receptor family.  

And that’s what makes domoic acid so dangerous. It mimics glutamic acid and overstimulates these receptors, especially in the brain. The result? Seizures, memory loss, disorientation, and in many cases, death. Some seals that survive the initial damage show profound changes in mental status—disoriented, aggressive, even attacking people on the beach.

What's going on?

Chances are you've guessed that this mess has something to do with toxic algae blooms and if so, you're right. They are bad news, especially for people and other life forms that happen to own receptors. 

But fish don’t seem to mind. They cheerfully survive blooms of the marine diatom Pseudo-nitzschia, the algae behind domoic acid production. These microscopic phytoplankton have repaid humanity for decades of ocean abuse by weaponizing a neurotoxin that climbs the food chain like a biochemical Trojan horse.

Here’s how it works: Filter-feeding fish like anchovies and sardines snack on Pseudo-nitzschia and store the domoic acid—mostly in their digestive tracts. They’re unfazed, of course, because fish lack the specific glutamate receptors that domoic acid targets. But the animals that gobble up the fish—seals, sea lions, seabirds, and occasionally people—get a dose of what you might call “pescatarian payback.”

Time for a chemistry lesson. Probably not much worse than a neurotoxin.

For this, pretty much like everything else, chemistry can provide an explanation. Figure 1, below, should (but probably won't) make it obvious.

Figure 1. Three excitatory amino acid. 

The pharmacophores [2] of domoic acid, kainic acid, and glutamic acid (aka glutamate) are very similar. Note that all three have a basic nitrogen, a three-carbon linker, and a two carboxylic acids, all in the same place. The numbers denote the carbon linker between carboxylic acids. The potency (binding) is domoic acid > kainic acid > glutamate. 

What the smelt is going on?

If you've stuck with me this long, the rest is pretty easy. Glutamic acid is one of the endogenous neurotransmitters responsible for exciting neurons. Like other neurotransmitters, it is a molecular switch and is essential for learning, memory, and brain development. But if the switch is damaged and the current stays on (Figure 2) then bad stuff happens. 

Figure 2. (Left) The binding of glutamate to the kainate receptor—a subset of glutamate receptors—opens the membrane channel, allowing ions to move in and out of the synapse as needed. This brief, reversible activation prevents continuous stimulation and protects the brain from overexcitation and excitotoxicity. (Right) Domoic acid binds much more tightly, keeping the ion channel stuck open and leading to toxic ion influx.

The entire explanation in something resembling English

• Normally, glutamate binds briefly to the kainate receptor, opens the ion channel, and then quickly detaches, allowing the channel to close. This is the on-off switch
• Domoic acid, however, binds much more tightly and stays attached longer, so the ion channel remains open.
• This causes too many ions, especially Na⁺ and Ca²⁺, to flood into the neuron, leading to over excitation and cell damage.
• This is why seals are getting sick and dying. Their ion channels are being locked in the open position.

Summary

So while fish shrug off domoic acid like it’s just another day at sea, animals with more sophisticated (and unfortunately more vulnerable) nervous systems pay the price. As algal blooms become more common, more neurotoxins will be created, and more neurological casualties will wash ashore. In the end, it’s not the toxin itself that’s so clever—it’s the way it hijacks a normal brain function and refuses to turn it off. A little molecular mimicry, and the switch gets stuck. Permanently.

NOTES:

[1]  This is why chemistry can make you crazy. Even though kainic acid is simply a more potent form of glutamic acid, it got its name in the 1950s when it was first isolated from a seaweed named Digenea simplex, also known in Japanese as “kainin-sō.” Natural products are frequently named from the source from which they were isolated.

[2] A pharmacophore is the set of essential chemical features of a molecule that interact with a specific biological target to trigger a response.