This week’s BEACON Researchers at Work blog post is by University of Texas at Austin graduate student Ben Liebeskind.
All life stores energy in the form of electrochemical gradients. These gradients drive nutrient uptake in bacteria, water uptake in plants, and power the formation of ATP in our mitochondria (which are actually derived bacteria). A few life forms have turned these gradients to a new purpose: electrical signaling. Electrical signals, like those in the brain, are well known in animals, but in fact many organisms control behavior using electrical signaling. The sparks emitted in the ocean by phosphorescent algae are set off by an electrical impulse called an action potential which largely resembles those that occur in our nervous systems. The closing of the Venus fly trap is also initiated by an action potential. Life, and behavior in particular, is electrical.
Ion Channels – the Transistors of the Brain
The Zakon Lab at the University of Texas studies the evolution and function of the proteins that give rise to these electrical impulses. These proteins, called ion channels, are like tiny holes in the membrane of the cells in which they reside; holes so small that only charged elements, called ions, can pass through. The movement of these tiny charges through ion channels can create electrical impulses so small we can barely measure them, or so large that, in the case of the electric eel, they can stun or even kill us. Ion channels propagate the electrical signals in nerves, and they also transduce the sensory signals of the world, like light or odorant molecules, into the electrical language of the nervous systems. The Hillis lab, also at the University of Texas, studies molecular evolution, phylogenetics, and broad questions about the systematics and diversity of life. Being co-advised by Drs. Zakon and Hillis, I approach the study of ion channels from an evolutionary perspective.
Evolution of Ion Channels – Lessons from the Deep Past
So when did these magical proteins evolve? Because all life must maintain electrochemical gradients, ion channels are found in the genomes of every type of organism, even viruses, which, not being cellular life forms themselves, have to steal the host cell’s lipid membrane before they can use the channels. So if all organisms have them, why is animal electrical signaling so complex relative to that of other organisms? This is a complex question, but I think we can start to formulate an answer by looking at ion channel evolution.
Many organisms use their electrical signals for two purposes at once: to stimulate the neighboring areas of the cell, thereby setting off a traveling electrical wave; and also as a means of rapidly delivering one key ion to the cell: Calcium. Calcium ions serve many purposes in cells. They trigger muscle contraction, regulate gene expression, trigger cell growth, and contribute to learning and memory in the brain. This great power is also a danger – too much calcium can trigger the cellular pathways that trigger cell death. Calcium overload is thought to be a major contributor to neuron death during a stroke. Organisms avoid this catastrophe by tightly limiting calcium intake. It is therefore hard to see how the nervous system could maintain its electrical activity using calcium ions alone. In fact, it doesn’t. Most electrical signals in our nervous system are carried by a different ion: Sodium – the same element that resides on your table as a salt. Sodium cannot trigger cell death; its sole purpose is to carry charges across the membrane. It also has the advantage of being abundant in the ocean, where early animals evolved. This is why the body maintains a salty internal environment, effectively carrying the ocean with us on land so we can maintain the environment in which our physiology first evolved. By employing sodium in this way, the nervous system can maintain a complex neural code that doesn’t poison its cells.
So when did sodium, rather than calcium channels, evolve? Now the story gets interesting. There appears to be no physiological evidence for sodium channels outside the animal kingdom, consistent with their specialized role in nervous systems. We have been able to show that the gene family actually arose long before the evolution of animals, but their function may initially have been different – they may perhaps have been calcium channels initially, and only later gained sodium selectivity in the animal lineage. By co-opting these genes for a new purpose, animals may have been able to develop their complex nervous sytems by running them on sodium.
Ion Channel Toxins – Terrible, Beneficial, Tasty?
Because of their centrality to nervous system function, ion channels are the targets of some of nature’s deadliest toxins. Organisms can create these toxins to quickly immobilize their prey or to cause searing pain in would-be predators. Many of these naturally occurring toxins have such a unique affinity for ion channels that they are used as research tools to selectively block or activate certain channel types. Several are used in medicine as well, for instance in the treatment of chronic pain. Perhaps the most famous ion channel toxin is the sodium channel blocker tetrodotoxin (TTX), named for the Tetraodontid pufferfish from which it was first isolated. This toxin occurs at low levels in pufferfish sushi, called Fugu – low levels, that is, if the chef is properly trained. Although pufferfish get the naming rights to this powerful toxin, the premier producer of TTX on land is the rough-skinned newt, Taricha granulosa. The newts, and the pufferfish as well, appear to be insensitive to their toxins, and several researchers study naturally occurring TTX resistance by looking at the sodium channels that are blocked by it. Interestingly, the newts also appear to be able to smell TTX in the water. The Zakon lab is involved in a collaboration with the Eisthen lab at Michigan State University to figure out how the newts have evolved this remarkable ability.
Ion channels create the language of the nervous system, and so we must understand them in order to understand ourselves. Not only that, but we they can give us insight into the private worlds of unique organisms, like the newts, or into organisms that existed in the deep past. This is only possible if we take a unique, interdisciplinary approach that combines molecular biology, neurobiology and biophysics, bioinformatics and computer science, and classical organismal biology. An interdisciplinary approach usually requires the input of many different scientists with different backgrounds, and BEACON facilitates this interaction by funding exploratory, interdisciplinary research, like ou
r newt study. Only in this integrative way can we hope to tackle the fascinating questions related to electrical life.
For more information about Ben’s work, you can contact him at bliebeskind at austin dot utexas dot edu.