For release: Wednesday, May 9, 2012
Auto engines, wind turbines and all manner of machines tend to operate less efficiently in the cold. Ion channels – the molecular machines that power nerve cell firing and muscle contraction – are no exception. That poses a challenge for animals that live in icy environments; to survive, they must adapt so that their ion channels can function at temperatures below freezing. In a study published in Science,* researchers have reported how one animal accomplishes this feat. Their work may shed light on the role of ion channels in human health and disease.
Bathypolypus arcticus. Credit: Sandra Garrett, University of Puerto Rico
The study was conducted by Joshua Rosenthal, Ph.D., an associate professor of neurobiology at the University of Puerto Rico, and Sandra Garrett, a graduate student in his lab. They chose to look at ion channel variations in different species of octopi, which can live in diverse climates. At first, they focused on two species, one from the balmy waters of Puerto Rico and another from the frigid seas of Antarctica.
The scientists searched for key differences in the animals' "delayed rectifier" potassium channels. These are gated pores that allow potassium to flow in and out of nerve cells; the flux of potassium is necessary for nerve cells to fire and is especially important for repetitive firing. Unlike mammals, octopi cannot generate their own body heat. So, without adjustment for the cold, the potassium channels of octopi in polar climates would be expected to open and close more slowly than their tropical counterparts. That would in turn alter the rate of nerve cell firing.
Because ion channels are proteins, which are made by genes, nature could have solved this problem through genetic mutation. But Dr. Rosenthal and Ms. Garrett found that the DNA codes for the potassium channels from polar and tropical species are nearly identical. Instead, they discovered that the channels are modified at the level of RNA, the intermediate chemical between DNA and proteins.
The researchers found that a process called RNA editing produces several small differences between the two channels. In the polar channel, a change to a single amino acid (the smallest building block for a protein) accelerates the rate at which the channel closes and thus helps compensate for the cold. This same editing site was found in potassium channels of several other octopus species, including two more tropical species, one from temperate waters, and two from the Arctic. The extent of editing was higher in species living in colder habitats.
"Species from the Arctic are editing these ion channels in the same manner as the Antarctic species on the opposite side of the world," said Dr. Rosenthal.
This is the first time that differences in RNA editing have been linked to differences in an animal’s environment – in this case, temperature. It is not yet known if an octopus can use RNA editing to rapidly adjust to changing temperatures, or if these editing differences evolve slowly over generations.
Beyond implications for how nervous systems adapt to unique environments, the findings could offer deep insights into human ion channels. Adaptive changes to ion channels, through RNA editing or other means, can point to sites within them that are functionally important across species, Dr. Rosenthal said. Such knowledge could lead to advances in understanding and treating a number of neurological disorders that have been linked to abnormal ion channel function. These "channelopathies" include some types of epilepsy and migraine.
Meanwhile, RNA editing has "huge unexplored potential" for human health, Dr. Rosenthal said. Compared to humans and other vertebrates (animals with a backbone), RNA editing appears to be more extensive in invertebrates (no backbone). However, every animal species appears to have a set of RNA-editing enzymes known as ADARs, according to Dr. Rosenthal.
With these enzymes, "nature is providing a system that can make genetic changes at the level of RNA. This may give us a novel approach to gene therapy," he said.
Dr. Rosenthal is investigating the potential of using RNA editing to treat a disorder called rapid-onset dystonia parkinsonism (RDP), which is caused by genetic mutations in a protein called the sodium-potassium pump. This pump works a bit like a battery, charging up nerve cells so that they can fire. In invertebrates, the sodium-potassium pump is fine-tuned by RNA editing. Dr. Rosenthal theorizes that it might be possible to treat RDP by stimulating human RNA-editing enzymes to repair the pump.
Dr. Rosenthal’s research is supported by NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and by the National Science Foundation. Ms. Garrett is supported by a pre-doctoral fellowship from NINDS.
- By Daniel Stimson, PhD.
*Garrett S and Rosenthal J. "RNA Editing Underlies Temperature Adaptation in K+ Channels from Polar Octopi." Science, February 17, 2012, Vol. 335, pp. 848-851.
Last Modified May 9, 2012