Stanford News

6/3/97

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Fast squid beats slow limpet with a speedy sodium channel

This is the tale of the tortoise and the hare ­ or rather the marine version, an evolutionary race between the limpet and the squid.

Two scientists set out to settle a friendly argument about what makes the limpet slower than a snail, while their distant cousin the squid is quick as a flash of temper. The scientists findings, published in the April issue of the Journal of Neurophysiology, show that part of the difference comes because squids evolved a faster way to fire off electrical nerve impulses.

The scientists' findings are helping to overturn the current thinking about how nerve impulses get started. Based on their study and the work of others, it appears likely that this may include the impulses in our own jangling nervous systems. The way neurons develop and connect to each other in a newborn baby, or the way nerve cells respond to therapy after an injury, depends partly on whether the cells contain the fast or the slow version of an electrical firing mechanism called a sodium channel.

Nobody could have been more surprised their findings than the scientists themselves. William Gilly, a Stanford associate professor of biology, studies squid to learn how the electrical firing pattern of nerve cells is controlled, and how nerve cells work together to control muscles and behavior. Among other things, Gilly is known for his work on sodium and other ion channels, the proteins responsible for electrical signaling in nerve and muscle cells.

University of Illinois neurophysiologist Rhanor Gillette is an expert on neurotransmitters, the chemicals that act as messengers between nerve cells. He uses sea slugs in his studies. To hear his friend Gilly tell the tale, Gillette has a fondness for some very slow animals ­ slugs, snails, even the slope-shelled limpets that cling to rocks in pounding waves. "It takes a trained ethological eye like Rhanor's to discriminate a limpet's behavioral repertoire from that of the rocks," Gilly said. Personally, Gilly prefers squid ­ sleek, jet-propelled, with lightning reflexes that react instantly to a sudden sign of danger or of prey.

The race is on

The race between the limpet and the squid began several years ago, when Gillette was planning a sabbatical at Stanford's Hopkins Marine Station. Over a bottle of a good California Merlot, he posed a question about sodium channels, the proteins that start each electrical nerve impulse.

Limpets and slugs and snails ­ all classified as gastropods ­ are seldom as swift as cephalopods like the squid and the octopus, but they are members of the same family tree. All are mollusks, and share a common evolutionary background. Could it be, Gillette asked Gilly, that the difference between speedy cephalopods and sluggish gastropods had something to do with their sodium channels, the proteins responsible for generating most nerve impulses? Perhaps slow mollusks evolved with slow-acting sodium channels, whereas fast mollusks have fast ones.

Not likely, said Gilly, the ion channels expert. "Sodium channels really did only one thing that I was sure of ­ propagate the nerve impulse ­ and they were the fastest of all channels in every organism ever studied, the big guys of excitability. Besides that, it seemed hard to believe that something as fundamental as nerve impulse transmission would be the limiting factor in how fast the muscles work."

Still, he had to admit that Gillette had an interesting hypothesis. A sodium channel is shaped something like a donut, stuck in the wall of a nerve cell with a "gate" that opens and shuts over the donut hole. That gate is controlled by a tiny amount of voltage ­ normally about a tenth of a volt ­ across the cell membrane. When the gate opens, positively charged sodium ions rush into the cell, generating a positive voltage that opens other sodium channel gates. This sets off an explosive sequence as the electrical charge propagates down the nerve cell's long axon.

"These impulses buzz inside your cranium like a million bees inside a peanut butter jar," Gilly said. "You could imagine that the faster these nerve impulses move around, and the higher the frequency of their occurrence, then the faster a brain could process information.

"Thus it made sense [at least to Gillette] that the gates in sodium channels should operate more rapidly in a fast animal than a slow animal," Gilly said. The fast-opening channels would be the equivalent of a speedier baud rate for a computer modem.

Working with graduate student Matt McFarlane, the scientists began testing this idea on a variety of fast and slow mollusks. "We'd arrange to catch the low tide and go down to the rocky beach of Monterey Bay, where we'd collect any snail or nudibranch that caught our eye," said Gillette. "Or we'd meet the trawl boats to see what they might have brought in, and ask our colleagues for interesting specimens they might be keeping in their aquaria. We would take the nervous systems of these animals and grow their nerve cells in culture to prepare them for electrical studies."

They used a relatively new and highly accurate device called a patch clamp to detect the reaction of sodium channels to small changes in voltage. Much to Gilly's chagrin ­ since they'd bet a bottle of wine on the outcome ­ the slow gastropods turned out to have sodium channel gates that flapped open at a much slower rate than the fast cephalopods.

Since the squid-versus-limpet study began, Gilly has discovered that some squid nerve cells also have some slow sodium channels. A search of the literature found that years ago, some types of snails showed what appeared to be slow sodium channels, but the technology at the time did not provide a way to refine those results. Meanwhile, since Gilly and Gillette began their experiment, several other research groups have used advanced patch-clamp technology to find slow sodium channels in other animals. Mammals ­ specifically laboratory rats ­ appear to have both fast and slow sodium channels in sensory neurons.

An evolutionary competition

The data all point to a need for biologists to re-think what sodium channels do and how they evolved. Gillette suspects that squids and other cephalopods evolved fast sodium channels as a necessary adaptation. "Squids evolved from quite sluggish mollusks into somewhat faster, swimming shell-wearing polyps, like the chambered Nautilus that bob around in the abyss. Then squid went on to the sleek modern versions that hunt in packs," he said. The research team tested Nautilus sodium channels and found them to be faster than snails, slower than squid. "The evolution of this faster type of current may have paralleled the Nautilus' acquisition of swimming behavior and image-forming eyes," he said.

"It is widely thought that squid evolution was driven by a competitive race with the vertebrate fish, many of whom were also evolving toward being fast swimmers and social, schooling predators," Gillette said. The squid's cousin the octopus is not as fast a swimmer, but it is thought to be one of the most intelligent animals in the sea. Part of faster swimming or faster thinking evidently involved speeding up the rate of electrical signaling in the brain and from the nervous system to the muscles, he said.

"Modern vertebrates also have very fast sodium channels, perhaps evolved by our fishy ancestors for faster swimming at the same time as the squid," Gillette said. "It's another escalation in the vertebrate-cephalopod competition that continues in the oceans today."

Gilly is convinced now that both fast and slow channels will be found in many animals, sometimes on the same nerve cell.

"The more complex a brain is, the more need there is for specialized slow and fast sodium channels," he said. Electrical impulses are transmitted along axons so several sections of the brain can coordinate a complex behavior. Fast sodium channels transmit these messages quickly over long distances, like a fast modem on a fiber-optic cable.

But most decisions at the level of the single nerve cell are made after integrating impulses from many inputs. It might be a disadvantage to have a nerve cell react too quickly to these signals, firing off a message before enough information has arrived, Gilly said.

No one knows for sure yet whether these findings have implications for humans. Gilly said he wouldn't be surprised if they do, since much of the fundamental understanding about how the human nervous system works has come from studies of squids and other animals. It now appears that fast and slow sodium channels in mammals are regulated differently as an embryo develops into an adult; so far, no one knows why. And Gilly speculates that slow and fast sodium channels may react differently following injury to nerve and muscle cells ­ a difference that might be significant for therapy.

"We need to figure out what the different channel types are doing in order to in order to understand the reasons," he said.

Gilly has long since paid off his debt of a bottle of wine, admitting that Gillette and his limpets won the bet ­ though he said that's the only race a gastropod is ever likely to win against a squid, at least underwater. He also admits to having gained a grudging respect for slow-moving animals like slugs. "They do not show much fast intelligence, but they still make plenty of decisions and show lots of interesting behavior."

For information about Rhanor Gillette's research see http://www.life.uiuc.edu/Biophysics/faculty/gillette.html

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By Janet Basu