Posts tagged sodium
Articles and news from the latest research reports.
International research collaboration reveals the mechanism of the sodium-potassium pump
It’s not visible to the naked eye and you can’t feel it, but up to 40 per cent of your body’s energy goes into supplying the microscopic sodium-potassium pump with the energy it needs. The pump is constantly doing its job in every cell of all animals and humans. It works much like a small battery which, among other things, maintains the sodium balance which is crucial to keep muscles and nerves working.
The sodium-potassium pump transports sodium out and potassium into the cell in a fixed cycle. During this process the structure of the pump changes. It is well-established that the pump has a sodium and a potassium form. But the structural differences between the two forms have remained a mystery, and researchers have been unable to explain how the pump distinguishes sodium from potassium.
Structure solves the mystery
Thanks to the international collaboration between Professor Chikashi Toyoshima’s group at the University of Tokyo and researchers from Aarhus University, the structure of the sodium-bound form of the protein has now been described. For the first time ever, the sodium ions can be studied at a resolution so high - 0.28 nanometres - that researchers can actually see the sodium ions and observe where they bind in the structure of the pump. In 2000, Professor Chikashi Toyoshima’s group described the structure of a calcium-pump for the first time, and in 2007 and 2009 research groups from Aarhus University and Toyoshima’s group described the potassium-bound form of the sodium-potassium pump.
"The new protein structure shows how the smaller sodium ions are bound and subsequently transported out of the cell, whereas the access of the slightly larger potassium ions is blocked. We now understand how the pump distinguishes between sodium and potassium at the molecular level. This is a great leap forward for research into ion pumps and may help us understand and treat serious neurological conditions associated with mutations of the sodium-potassium pump, including a form of Parkinsonism and alternating hemiplegia of childhood in which sodium binding is defective," explains Bente Vilsen, a professor at Aarhus University who spearheaded the project’s activities in Aarhus with Associate Professor Flemming Cornelius.
Impressed Nobel Prize winner
The vital pump was discovered in 1957 by Professor Jens Christian Skou of Aarhus University, who received the Nobel Prize for his discovery in 1997. The new result is the culmination of five or six decades of research aimed at the mechanism behind this vital motor of the cells.
"Years ago, when the first electron microscopic images were taken in which the enzyme was but a millimetre-sized dot at 250,000 magnifications, I thought, how on earth will we ever be able to establish the structure of the enzyme. The pump transports potassium into and sodium out of the cells, so it must be capable of distinguishing between the two ions. But until now, it has been a mystery how this was possible," says retired Professor Jens Christian Skou, who - even at 94 years of age - keeps up to date with new developments in the field of research which he initiated more than 50 years ago.
"Now, the researchers have described the structure that allows the enzyme to identify sodium and this may pave the way for a more detailed understanding of how the pump works. It is an impressive achievement and something I haven’t even dared dream of," concludes Jens Christian Skou.
(Source: eurekalert.org)
A new role for sodium in the brain
Researchers at McGill University have found that sodium – the main chemical component in table salt – is a unique “on/off” switch for a major neurotransmitter receptor in the brain. This receptor, known as the kainate receptor, is fundamental for normal brain function and is implicated in numerous diseases, such as epilepsy and neuropathic pain.
Prof. Derek Bowie and his laboratory in McGill’s Department of Pharmacology and Therapeutics, worked with University of Oxford researchers to make the discovery. By offering a different view of how the brain transmits information, their research highlights a new target for drug development. The findings are published in the journal Nature Structural & Molecular Biology.
Balancing kainate receptor activity is the key to maintaining normal brain function. For example, in epilepsy, kainate activity is thought to be excessive. Thus, drugs which would shut down this activity are expected to be beneficial.
“It has been assumed for decades that the “on/off” switch for all brain receptors lies where the neurotransmitter binds,” says Prof. Bowie, who also holds a Canada Research Chair in Receptor Pharmacology. “However, we found a completely separate site that binds individual atoms of sodium and controls when kainate receptors get turned on and off.”
The sodium switch is unique to kainate receptors, which means that drugs designed to stimulate this switch, should not act elsewhere in the brain. This would be a major step forward, since drugs often affect many locations, in addition to those they were intended to act on, producing negative side-effects as a result. These so called “off-target effects” for drugs represent one of the greatest challenges facing modern medicine.
“Now that we know how to stimulate kainate receptors, we should be able to design drugs to essentially switch them off,” says Dr. Bowie.
Dr. Philip Biggin’s lab at Oxford University used computer simulations to predict how the presence or absence of sodium would affect the kainate receptor.
(Source: mcgill.ca)
Simulated Mars Mission Reveals Body’s Sodium Rhythms
Clinical pharmacologist Jens Titze, M.D., knew he had a one-of-a-kind scientific opportunity: the Russians were going to simulate a flight to Mars, and he was invited to study the participating cosmonauts.
Titze, now an associate professor of Medicine at Vanderbilt University, wanted to explore long-term sodium balance in humans. He didn’t believe the textbook view – that the salt we eat is rapidly excreted in urine to maintain relatively constant body sodium levels. The “Mars500” simulation gave him the chance to keep salt intake constant and monitor urine sodium levels in humans over a long period of time.
Now, in the Jan. 8 issue of Cell Metabolism, Titze and his colleagues report that – in contrast to the prevailing dogma – sodium levels fluctuate rhythmically with 7-day and monthly cycles. The findings, which demonstrate that sodium is stored in the body, have implications for blood pressure control, hypertension and salt-associated cardiovascular risk.
Titze’s interest in sodium balance was sparked by human space flight simulation studies he conducted in the 1990s that showed rhythmic variations in sodium urine excretion.
“It was so clear to me that sodium must be stored in the body, but no one wanted to hear about that because it was so different from the textbook view,” he said.
He and his team persisted with animal studies and demonstrated that the skin stores sodium and that the immune system regulates sodium release from the skin.
In 2005, planning began for Mars500 – a collaboration between Russia, the European Union and China to prepare for manned spaceflight to Mars. Mars500 was conducted at a research facility in Moscow between 2007 and 2011 in three phases: a 15-day phase to test the equipment, a 105-day phase, and a 520-day phase to simulate a full-length manned mission.
Crews of healthy male cosmonauts volunteered to live and work in an enclosed habitat of sealed interconnecting modules, as if they were on an international space station. Titze and his colleagues organized the food for the mission and secured commitments from the participants to consume all of the food and to collect all urine each day. They studied twelve men: six for the full 105-day phase of the program, and six for the first 205 days of the 520-day phase.
“It was the participants’ stamina to precisely adhere to the daily menu plans and to accurately collect their urine for months that allowed scientific discovery,” Titze said. The researchers found that nearly all (95 percent) of the ingested salt was excreted in the urine, but not on a daily basis. Instead, at constant salt intake, sodium excretion fluctuated with a weekly rhythm, resulting in sodium storage. The levels of the hormones aldosterone (a regulator of sodium excretion) and cortisol (no known major role in sodium balance) also fluctuated weekly.
Changes in total body sodium levels fluctuated on monthly and longer cycles, Titze said. Sodium storage on this longer cycle was independent of salt intake and did not include weight gain, supporting the idea that sodium is stored without accompanying increases in water.
The findings suggest that current medical practice and studies that rely on 24-hour urine samples to determine salt intake are not accurate, he said. “We understand now that there are 7-day and monthly sodium clocks that are ticking, so a one-day snapshot shouldn’t be used to determine salt intake.”
Using newly developed magnetic resonance imaging (MRI) technologies to view sodium, Titze and his colleagues have found that humans store sodium in skin (as they found in their animal studies) and in muscle.
The investigators suspect that genes related to the circadian “clock” genes, which regulate daily rhythms, may be involved in sodium storage and release. “We find these long rhythms of sodium storage in the body particularly intriguing,” Titze said. “The observations open up entirely new avenues for research.”
Ion selectivity in neuronal signaling channels evolved twice in animals
July 26, 2012
Excitation of neurons depends on the selected influx of certain ions, namely sodium, calcium and potassium through specific channels. Obviously, these channels were crucial for the evolution of nervous systems in animals. How such channels could have evolved their selectivity has been a puzzle until now. Yehu Moran and Ulrich Technau from the University of Vienna together with Scientists from Tel Aviv University and the Woods Hole Oceanographic Institution (USA) have now revealed that voltage-gated sodium channels, which are responsible for neuronal signaling in the nerves of animals, evolved twice in higher and lower animals. These results were published in Cell Reports.
Close-up of nervous system of a transgenic polyp of the sea anemone Nematostella vectensis, in which a red fluorescent reporter gene (mCherry) is driven by the regulatory sequence of the neuronal ELAV gene. The picture shows the diffuse structure of the nervous system, but also reveals the accumulation of longitudinal axonal tracts along the eight gastric tissue folds (mesenteries). Credit: Copyright: U. Technau
The opening and closing of ion channels enable flow of ions that constitute the electrical signaling in all nervous systems. Every thought we have or every move we make is the result of the highly accurate opening and closing of numerous ion channels. Whereas the channels of most lower animals and their unicellular relatives cannot discern between sodium and calcium ions, those of higher animals are highly specific for sodium, a characteristic that is important for fast and accurate signaling in complex nervous system.
Surprising results in sea anemones and jellyfish
However, the researchers found that a group of basal animals with simple nerve nets including sea anemones and jellyfish also possess voltage-gated sodium channels, which differ from those found in higher animals, yet show the same selectivity for sodium. Since cnidarians separated from the rest of the animals more than 600 million years ago, these findings suggest that the channels of both cnidarians and higher animals originated independently twice, from ancient non-selective channels which also transmit calcium.
Since many other processes of internal cell signaling are highly dependent on calcium ions, the use of non-selective ion channels in neurons would accidently trigger various signaling systems inside the cells and will cause damage. The evolution of selectivity for sodium ions is therefore considered as an important step in the evolution of nervous systems with fast transmission. This study shows that different parts of the channel changed in a convergent manner during the evolution of cnidarians and higher animals in order to perform the same task, namely to select for sodium ions.
This demonstrates that important components for the functional nervous systems evolved twice in basal and higher animals, which suggests that more complex nervous systems that rely on such ion-selective channels could have also evolved twice independently.
Source: PHYS.ORG