By: Brandon Keim
Most people know that nerves work by passing electrical currents from cell to cell. But you might be surprised to learn that no one knows exactly how anesthetics stop nerves from carrying pain signals.
That's why two scientists believe that we really don’t know how nerves work after all.
According to their controversial theory, electricity is just a side effect of how nerves really operate: by conducting high-density waves of pressure that resemble sound reverberating through a pipe.
"Nerves are supposed to work like a series of electrical transistors," said Andrew Jackson, a physicist at the Niels Bohr Institute in Copenhagen, Denmark. "This picture is at best flawed."
If correct, Jackson and Thomas Heimburg, a Niels Bohr biophysicist and co-author of a recent paper describing their theory, would turn a long-held (and Nobel Prize-winning) theory on its head.
Alan Hodgkin and Andrew Huxley won the Nobel Prize in physiology or medicine in 1963 for describing the electric transmission of impulses along nerves -- a now widely accepted theory known as the Hodgkin-Huxley model.
But Jackson and Heimburg say that the inability to explain how anesthesia works, combined with other counterintuitive aspects of the theory, mean that nerves don't rely on electricity to carry messages.
For example, the Hodgkin-Huxley model still hasn't accounted for observations made a century ago by scientists Hans Meyer and Charles Overton. They demonstrated that the strength of an anesthetic could be predicted by its solubility in olive oil rather than its chemical structure. The more soluble the anesthetic, the stronger it was.
Since olive oil is similar to the lipid molecules that make up nerve cells, Jackson and Heimburg started questioning the generally accepted belief that anesthetics block electrical pulses by fitting themselves into pain receptors on cells. That seems next to impossible, they said, because anesthetic molecules come in many shapes and sizes, and it's difficult to imagine that they all happen to physically fit into all receptors.
"That is about as likely as tossing a coin 1,000 times and having it come down heads every time," Jackson said.
Their theory, published in the Biophysical Journal, explains how nerves and anesthetics work as follows: Nerves are made of lipids that are liquid at body temperature. A yet-to-be-defined mechanism creates high-pressure, semisolid waves that move through the cells, delivering messages.
Anesthetics, they suggest, lower the temperature at which lipids become solid, making it difficult for the waves to form, thereby preventing nerves from sending pain signals. They also suggest that as the waves travel, they change the shape of the cell membrane, producing the electrical pulse that scientists currently mistake for the primary function of nerve cells.
The theory has not been well received. Few are convinced that the inexplicability of anesthetics is reason to dismiss the Hodgkin-Huxley model. One molecular biologist and ion channel expert even refused to comment on record about the theory because he found it too preposterous.
"The fact that we don't know how anesthetics work make it a nice target for anybody with a new hypothesis," said Roderic Eckenhoff, a University of Pennsylvania molecular pharmacologist. "But the Hodgkin-Huxley model has been pretty well vetted."
The mystery of anesthetics, however, is not the only inconsistency that Jackson and Heimburg point out.
Another example is the fact that as electricity travels through the nerve, heat is released and then reabsorbed. This, said Jackson, contradicts the known behavior of electrical currents through a resistor.
"The heat generated by such a process is dissipated and not reabsorbed," he said.
Scientists say that until Jackson and Heimburg can provide empirical data to support their theory, it will remain a fringe idea.
"I appreciate the place for theory in advancing science, but the weight of evidence is soundly on the side of electricity," said Eckenhoff. "When they provide some experimental evidence consistent with their theory, that'd be great."
Jackson and Heimburg say that's exactly what they're hoping will follow the publication of their theory. "We hope that people will investigate the possibility," Jackson said.
If it turns out they're right, he said, "We might be able to help design cures for neurological problems and design better anesthetics."
Meanwhile, the duo admit they very well might be wrong, but they believe their theory is worth testing.
"We might be wrong," Jackson said, "but we're not crazy."
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Monday, June 11, 2007
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