Some tips for better hydration for athletes:

"After a long cold Spring and no chance to acclimate to heat, runners should push a lot of water and sodium from the very start of an ultra.

1. Drink water and take some salt BEFORE the race begins. Race Directors will please provide, water AND CUPS at the start line.

2. You need 400 to 800 mgm of sodium per hour under hot conditions. The average small pretzel or saltine found at the aid stations has only 30 mgm of sodium. If you're drinking water only, you'd need 13 of those per hour to get in enough sodium. Even if you're taking a sportsdrink, one or two pretzels may not be enough. Most drinks are on the low side of the sodium requirement because the drinks would taste like sea water if they had sodium levels equivalent to 800 mgm/hour.

3. Colas typically contain little or no sodium. A steady diet of half cola, half water could lead to inadequate sodium in a few hours of running.

4. Don't be fooled by running in dry weather. Sweat may evaporate so fast that you think you're not sweating much when in fact you're sweating a great deal, and losing water through your lungs as you exhale.

5. Don't assume that you are hydrated if you pee late in a run. If you are low on sodium, your body will be forced to dump water to keep you from going into a state of hyponatremia ( low sodium ). Thus it is possible to be dehydrated and peeing at the same time.

6. If you do get dehyrated, take salt and water together. Your body will not properly re-hydrate if you don't have sodium on board. Therefore, avoid soda and sparkling waters unless you also take sodium.

7. Don't trust your sense of thirst in an ultra. Most people are actually dehydrated by the time they register as thirsty.

8. If you do get dehydrated, your blood pressure will be low. If you jump into a hot shower after the run, the blood vessels near the skin will dilate and your blood pressure will drop so low that your heart cannot push blood to the brain for a few seconds and you will pass out in the shower. If you need to clean up, use a wash cloth wet with tepid water.

9. If you feel dizzy or have a queasy stomach, slow down or sit for a while. If it is really hot, you weren't going to have a PR anyway, so why kill yourself to finish a few minutes sooner?

10. The runners most in danger of dehydration are not the speedsters at the front of the race, but those at the back of the pack who spend more hours out in the heat.

11. If there is ice at the aid stations, consider wearing a white, mesh cap in which you can put ice cubes. It may look silly, but may also help cool your head a lot. It worked wonders for me at the hot, humid '94 Vermont 100.

I will echo the statement: it is just as stressful to be Race Director on a bad day as it is to run."

http://www.ultrunr.com/hydrate.html

Hope you found this helpful.

-Joshua

"Nations who still practice it "should feel ashamed of themselves"

Water Fluoridation "Obsolete" According to Nobel Prize Scientist Nations who still practice it "should feel ashamed of themselves" On October 4, 2005, two members of the Fluoride Action Network — Michael Connett and Chris Neurath — traveled to Gothenburg, Sweden, to interview Dr. Arvid Carlsson, a famed pharmacologist at Gothenburg University and recent winner of the Nobel Prize in Medicine/Physiology. In the 1970s, Dr. Carlsson was an outspoken opponent of two failed attempts to fluoridate water supplies in Sweden. Thanks in large part to his efforts, Sweden remains fluoridation free. As Carlsson notes, "nobody talks about [fluoridation] anymore" in Sweden. As with the vast majority of western Europe, Sweden has rejected water fluoridation, but has still experienced the same decline in tooth decay as experienced in heavily fluoridated countries such as the United States. Video Clips of Interview — Quicktime required Clip 1: Fluoridation 'Obsolete' — [broadband | dial-up] Clip 2: No reason to ingest fluoride — [broadband | dial-up] Clip 3: Responding to CDC — [broadband | dial-up] Excerpts of Interview with Dr. Arvid Carlsson, October 4, 2005 CONNETT: So, what happened in Sweden. The fluoridation issue was proposed… CARLSSON: Yes, I think it was up twice… The second time, there was a proposal that the Swedish Parliament should allow addition of fluorine to the water supplies in Sweden and I became rather active as I had been the first time, and I think I was perhaps the one who more than anyone else convinced the Swedish parliament that this was not a good thing. So, it was voted out, this proposal. And that was around 1980. So you can see it's a long time ago. And after that addition of fluorine to water supplies in Sweden has not been an issue anymore. These days nobody talks about it anymore. ### CONNETT: Do you think that your background in pharmacology sort of informed your view of fluoridation as a medical practice? CARLSSON: Of course. I mean, as I said before, this is against all principles of modern pharmacology. It's really obsolete. No doubt about that. I mean, I think those nations that are using it should feel ashamed of themselves. It's against science. Anti-scientific. ### CARLSSON: Fluorine has a protecting action against caries, but this is a local effect… If you drink it, you are running the risk of all kinds of toxic actions. And, of course, there are such actions. We have the mottled teeth, which is not a small thing… There is no need, really, to go any further into all these other toxicity problems because I think the mottled teeth is enough. This is something you shouldn't expose citizens to. CONNETT: In the United States, the dental community says that dental fluorosis is just a cosmetic effect, it's just spots on the teeth. Do you see mottled teeth as a toxic effect of fluoride, or as simply a cosmetic effect? CALRSSON: Well, it is a toxic effect and a cosmetic effect. These are not mutually exclusive. It's toxic and it's cosmetic. ### CONNETT: What about this notion of using the water supply as a vehicle of delivering medication? Can you speak to what you see as the problems with that? CARLSSON: Yea, it's absolutely obsolete. In modern pharmacology it's so clear that even if you have a fixed dose of a drug, the individuals respond very differently to one and the same dose. Now, in this case, you have it in the water and people are drinking different amounts of water. So you have huge variations in the consumption of this drug. So, it's against all modern principles of pharmacology. It's so obsolete, I don't think anybody in Sweden, not a single dentist, would bring up this question in Sweden anymore. ### CONNETT: You mentioned that fluoride's benefits come from the local, or topical, effect. Could you just discuss a little more what you see as the significance of that fact? Why is it important that fluoride's benefit is topical, and not from ingestion? CARLSSON: Well, in pharmacology, if the effect is local, it's of course absolutely awkward to use it in any other way than as a local treatment. I mean this is so obvious. You have the teeth there, they're available for you, why drink the stuff?… I see no reason at all for giving it in any other way than locally — topically, if you wish. ### CONNETT: In the US, the Centers for Disease Control, which is a US government health body, has proclaimed water fluoridation to be one of the top ten public health achievements of the twentieth century. CARLSSON: I disagree profoundly."

http://www.fluoridealert.org/carlsson-interview.html

This is such an important issue in the US. I feel lucky to live in one of the only cities in the US that doesn't flouridate their water. It really seems crazy that we the people of this country can let this go on… What do you think? Let me know by posting your comments here.

-Joshua

"Overhead view of an ion channel. Image courtesy of Brookhaven National Lab Two American scientists shared the 2003 Nobel Prize in Chemistry for making key discoveries concerning how water and ions are transported through cell membranes. Peter Agre of the Johns Hopkins School of Medicine was honored for isolating a cell membrane protein that serves as a channel for transporting water. Roderick MacKinnon of the Howard Hughes Medical Institute at The Rockefeller University was recognized for determining the spatial structure and workings of ion channels, which transport ions through cell walls and allow cells to generate and transmit electrical signals. Agre and MacKinnon's research is important not only for contributing to fundamental chemical knowledge of how cells function, but also for the potential medical applications their discoveries might enable. Diabetes and other serious diseases of the nervous system, muscles, and heart can be attributed to malfunctioning cellular water and ion channels. By understanding how cell channels, gates, and valves are necessary for the cell to function, Agre and MacKinnon have provided a foundation for developing more effective pharmaceuticals.  (See this week's other feature articles for more information on the physics and medicine prizes and on all three science prizes.) Water Channels It was understood since the mid-19th century that there must be openings in the cell membrane to permit the passage of water and salts in order for the cells to maintain even pressure and function properly. But the appearance and function of these openings, or pores, remained a mystery until the late 1980s when Agre discovered the first water channel. Until Agre's discovery, the very concept of water-specific channels was somewhat controversial, although research performed in the late 1950s showed that water is rapidly transported through red blood cell membranes via channels that exclude ions and other solutes. Studies over the next 30 years suggested that water channels enable ordinary water molecules to flow freely (to the tune of a billion H2O molecules per second per channel) while blocking the flow of water molecules with an extra proton, or hydrogen ion, attached (H3O+). Agre was able to identify the protein that formed the actual channel.He studied various membrane proteins in red blood cells, and he later found one of these membrane proteins of unknown function in the kidney. He determined its peptide sequence and its corresponding DNA sequence and then realized this membrane protein (CHIP28) might form the elusive water channel. Agre performed a simple experiment in which he compared cells that had the CHIP28 protein with cells which did not have it. When the cells were placed in an aqueous solution, the cells that had the protein in their membranes swelled rapidly through osmosis while the cells that lacked the protein were not affected at all. The same phenomenon was observed when Agre performed experiments with liposomes, synthetic spheres that mimic the structure of cells. Agre named the protein aquaporin, or water pore. In 2000, together with other research teams, Agre reported the first high-resolution images of the 3D structure of aquaporin. Since his discovery, aquaporin-like proteins have been found in plants, animals, and bacteria. In humans alone, there are at least 11 different aquaporin-like proteins, many of which have been connected to assorted diseases. Ion Channels In 1998, MacKinnon stunned the research community by determining the first high-resolution structure of an ion channel from the bacterium Streptomyces lividans, revealing how an ion channel works at the atomic level. He could also explain why potassium ions (K+) but not sodium ions (Na+)—which are smaller—are admitted through a specific channel. The foundation for MacKinnon's breakthrough was laid by other Nobel laureates. Wilhelm Ostwald proposed in 1890 that the electrical signals measured in living tissue could be caused ions moving through cell membranes. Then, in the 1950s, two British scientists, Alan Hodgkin and Andrew Huxley showed how ions moving through cell membranes produced a signal that is transmitted from cell to cell. Research during the 1970s determined that ion channels were selective, admitting certain ions (primarily K+ and Na+) because they were equipped with an ion filter. They suspected that the oxygen atoms in the protein acted as a substitute for the water solution from which K+ must free itself during entry of the ion channel. MacKinnon confirmed this hypothesis and proved how the ions passed through the channel. In a series of crystal structures, MacKinnon saw the ions surrounded by water molecules just before they entered the ion filter, became stripped of their water and allowed to pass through the filter, and then met the water on the other side of the filter. MacKinnon also explained why the filters are selective: for each ion, the distance to the oxygen atoms in the ion filter is the same as in its water solution, therefore the smaller sodium ion cannot be freed from its water and pass through a larger potassium ion filter."

"Dennis_Loney"

http://chemistry.org/portal/a/c/s/1/feature_tea.html?id=c373e9f834410ea58f6a4fd8fe800100

Another good summary of the 2003 Nobel Prize winning research.

-Joshua

Imagine drinking a particular type of water and having your body suck up the water so well that it actually made your body more hydrated - with the same amount of water you were drinking before.

Well the new 50 person 30 day hydration study has just been completed and the results were surprising even to me. Not that I wasn't confident in how well this product works but an average increase in hydration of 23.5% among 50 people means that many of these folks experienced even higher than 23.5% (and some less) and that all 50 of these participants saw a significant effect from using this product.

Keep it in mind that these individuals did not know what the StirWand was. They had no preconceived knowledge of what was going on in this study. They simply followed directions and drank water stirred with the Stirwand.

The report from the study is posted on the main page here >> water hydration

Post your comments and questions here on the blog so I can answer them quickly for you.

(if you don't see the comment form simply click the title of this post (or any other post) and that page will have a comment form)

Thanks for visiting,

-Joshua

"Biochemists aren't much accustomed to seeing their work in the popular press, save for annual coverage of the Nobel prize in chemistry. This year, Roderick MacKinnon was recognized for working out the atomic structure of an ion channel and Peter Agre for discovering that a major protein found in red blood cells functions primarily as a water channel. Agre went on to establish the family of related channels, which he named "aquaporins." Channel proteins have aqueous pores that cross the cell membrane and regulate the flow of molecules in and out of cells. Water passively pours though aquaporins by osmosis, moving from low to high concentrations of solutes. Solving the structure of these channels provided a platform for exploring the underlying molecular mechanisms that allow the proteins to function as filters and maintain osmotic equilibrium. Robert Stroud and colleagues recently solved the atomic structure of an aquaporin (GlpF) and have now solved the structure of another water channel from Escherichia coli, called aquaporin Z, that selectively conducts only water at high rates.

Structure of aquaporin Z

Aquaporins form a large, diverse family of proteins and have been found in bacteria, plants, and animals. There are 11 family members in the human proteome. Less than a decade ago, scientists discovered the aquaporin Z gene (aqpZ) in E. coli, pointing to the protein's role in regulating water transport in this prokaryote. The high-resolution X-ray structures of recombinant aquaglyceroporin glycerol facilitator (GlpF)—a channel protein that transports both glycerol and water in E. coli—determined by the Stroud group in 2000 and of bovine aquaporin 1 (AQP1) from red blood cells, determined a year later, revealed how these aquaporins regulate their transport and selectivity. The aquaporin Z channel protein in E. coli can accommodate a flow of water at rates six times higher than GlpF, making it the prime subject for studying the selectivity of a high-conducting water channel. And because the two main classes of aquaporins occur in E. coli—which means they're exposed to the same cellular environment—and were both expressed recombinantly, the opportunities for comparative structural and functional analyses, combined with site-directed mutagenesis, promise to provide valuable insights into the molecular underpinnings of the selectivity of functionally different aquaporins.

After fabricating and growing a recombinant form of AqpZ in E. coli, David Savage in the Stroud group recovered the proteins from the bacterial colonies, then purified and concentrated them. The proteins were crystallized—capturing five water molecules inside—and then analyzed by state-of-the-art high-resolution X-ray diffraction techniques. The architecture of aquaporin Z, the researchers report, is typical of aquaporins, with a spiral of eight oxygens providing water-binding sites inside the channel and amino acid side chains determining the size and chemistry of the channel. The outer membrane and cytoplasmic ends of the channel are wider than the interior, which is long and narrow. This structure confirms that aquaporin selectivity arises in part from erecting a physical barrier: small molecules, like water, can easily pass, but larger ones simply can't fit. And the strategic positioning of amino acid residues with hydrophilic or hydrophobic properties along the channel helps police the influx of molecules based on their affinity for water. While it seems two amino acid chains located in the middle of the channel also provide a water-friendly surface, Stroud et al. say they play a more intriguing role. Noting that the water molecules occupy the channel in single file, the scientists explain that such an orientation would normally facilitate the random flow of protons (or hydrogen ions), which would be lethal to the cell. This central amino acid pair, they say, restricts the behavior of water molecules in the center of the channel in such a way that prevents "proton jumping" yet keeps the water flowing.

With two structural models of aquaporins down to the atomic level in the same species, scientists can now begin to investigate the molecular mechanisms that facilitate their selectivity. The importance of understanding these widely distributed channel proteins was underscored by the Nobel awards this year. Water transport is fundamental to life, and aquaporins are found throughout the body. Knowledge of their structure will help reveal the molecular mechanics of their specialized feats and promise to offer insights into a wide range of human disorders."

http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0000075

This is one of my favorite summaries of the Nobel Prize winning work in chemistry for Aquaporins. Let me know what you think about it by posting here.

-Joshua

"Princeton NJ — Princeton hydrologist Ignacio Rodriguez-Iturbe has been selected to receive the Stockholm Water Prize, a $150,000 award known informally as the "Nobel Prize of water."

Ignacio Rodriguez-Iturbe

King Carl XVI Gustaf of Sweden will present the award on behalf of the Stockholm Water Foundation at a ceremony in the Stockholm City Hall on Aug. 15.

The Stockholm Water Foundation, which has given the award annually since 1991, selected Rodriguez-Iturbe for his many contributions to the basic understanding of how water cycles between the oceans, the atmosphere and the continents. His work has ranged from discovering principles that govern the shape of all river basins to explaining the forces that drive cycles of floods and droughts.

"The cycle of water dramatically impacts all human activities," said Rodriguez-Iturbe, who holds the Theodora Shelton Pitney Professorship in Environmental Sciences. "From the water we drink and depend on for survival; to the rivers that provide clean and renewable energy; to the beauty of nature we enjoy in so many ways; to the weather that affects our lives — and so many other things — all are inseparably linked to hydrology."

The Stockholm Water Prize is given to scientists in a wide range of disciplines related to water, from marine chemistry to water management policy. According to the Stockholm Water Foundation, the prize "recognizes outstanding research, action or education that increases knowledge of water as a resource and protects its usability for all life." The recipient can be an individual, institution, organization or company.

"It is a wonderful prize and I am honored to receive it," said Rodriguez-Iturbe, who has joint appointments in the Department of Civil and Environmental Engineering and the Princeton Environmental Institute, where he currently serves as acting director.

"Professor Rodriguez-Iturbe is widely recog-nized by his peers as the worldwide intellectual leader of the field of surface water hydrology," said Peter Jaffe, chair of civil and environmental engineering. "He is an incredibly creative person who is knowledgeable over the whole scientific field. His research combines superb mathematical expertise with deep scientific knowledge, practical experience, imagination and originality. And he has an ability to reach across disciplines, such as geology, biology and physics. He also is a very warm person and great colleague."

Rodriguez-Iturbe joined the Princeton faculty in 1999 after holding positions at several institutions in the United States and in his native country of Venezuela.

In the decades since he received his 1967 Ph.D. from Colorado State University, Rodriguez-Iturbe has focused much of his work on discerning and explaining patterns in complex water systems. He helped establish, for example, that river basins, despite their infinite variety of shapes and forms, have a common structure in their two- and three-dimensional organization.

That research is among his most gratifying discoveries, Rodriguez-Iturbe said, noting that "understanding the dynamics behind this organization is of great importance for a truly scientific management of a river basin and of the resources it embodies."

He has applied his expertise in service to private and government agencies throughout the world, including leadership of an agency in Venezuela that balances environmental considerations with demand for hydroelectric power for one of the largest dam projects in the world.

Another key finding was the discovery that self-reinforcing cycles of moisture between land and air cause a tendency for weather systems to become stuck in extremes of drought or flood. Such concepts are valuable in predicting weather and climactic patterns. "These wet and dry modes tend to be persistent, and thus, the longer a drought has been going, the more likely it is that it will persist even longer," he said.

In all his work, a driving force has been simple curiosity. "The strongest motivation is a profound desire to understand how nature works," he said. "When I walk through forests or savannas in different ecosystems, or see the drainage network of a river from an airplane seat, or sense that a dry spell seems to go on longer than anyone expected — I ask myself, 'Why? What is behind all this?'"

Most recently, Rodriguez-Iturbe has begun to investigate how hydrology interacts with plant and animal life, helping to define the emerging field of eco-hydrology. Once again, he has begun to find patterns that may help to answer critical questions about the global environment and its all-important water resources.

He also has worked hard to convey the excitement of discovery to students. At Princeton, he created a course called "The Fractal Beauty of Landscapes" in which he introduced non-scientists to the concept of patterns that occur in nature."

"Steven Schultz"

http://www.princeton.edu/pr/pwb/02/0401/2a.shtml

Did you know there was a "Nobel Prize of Water"? Not the official Nobel Prize but still pretty impressive and interesting. What do you think?

-Joshua

"The cells signal with salt!
The first physical chemist, the German Wilhelm Ostwald (Nobel Prize in Chemistry 1909) proposed in 1890 that the electrical signals measured in living tissue could be caused by ions moving in and out through cell membranes. This electro-chemical idea rapidly achieved acceptance. The notion of the existence of some type of narrow ion channel arose in the 1920s. The two British scientists Alan Hodgkin and Andrew Huxley made a major breakthrough at the beginning of the 1950s and for this were awarded the Nobel Prize in Physiology or Medicine in 1963. They showed how ion transport through nerve cell membranes produces a signal that is conveyed from nerve cell to nerve cell like a relay race baton. It is primarily sodium and potassium ions, Na⁺ and K⁺, that are active in these reactions.

Thus as much as fifty years ago there was well-developed knowledge of the central functions of the ion channels. They had to be able to admit one ion type selectively, but not another. Likewise, it had to be possible for the channels to open and shut and sometimes to conduct ions in one direction only. But how this molecular machinery really worked was long to remain a mystery.

Ion-selective channel
During the 1970s it was shown that the ion channels were able to admit only certain ions because they were equipped with some kind of "ion filter". Of particular interest was the finding of channels that admit potassium ions but not sodium ions – even though the sodium ion is smaller than the potassium ion. It was suspected that the oxygen atoms in the protein played an important role as "substitutes" for the water molecules with which the potassium ion surrounds itself in the water solution and from which it must free itself during entry to the channel.

But further progress with this hypothesis was difficult – what was now needed was simply high-resolution pictures of the type only X-ray crystallography can provide. The problem was that it is extremely difficult to determine the structure of membrane proteins with this method, and the ion channels were no exception. Membrane proteins from plants and animals are more complicated and difficult to work with than those from bacteria. Using bacterial channel proteins that resemble human ion channels as closely as possible might perhaps offer a way forwards.

Many researchers tried in vain. The breakthrough came from an unexpected direction. Roderick MacKinnon, after studying biochemistry, turned to medicine and qualified as medical doctor. After working as a physician for some years, he grew so interested in ion channels that he started to do research in the field: "My scientific career in effect began at the age of 30", he has admitted. But his career took off quickly. Realising that better and higher-resolution structures were needed for understanding how ion channels function, he decided to learn the fundamentals of X-ray crystallography. It was then only a few years before he astonished the whole research community by presenting a structure of an ion channel. This was in April 1998.

First ion channel mapped – atom by atom
In 1998, then, MacKinnon determined the first high-resolution structure of an ion channel, called KcsA, from the bacterium Streptomyces lividans. MacKinnon revealed for the first time how an ion channel functions at atomic level. The ion filter, which admits potassium ions and stops sodium ions, could now be studied in detail. Not only was it possible to unravel how the ions passed through the channel, they could also be seen in the crystal structure – surrounded by water molecules just before they enter the ion filter; right in the filter, and when they meet the water on the other side of the filter (fig. 4). MacKinnon could explain why potassium ions but not sodium ions are admitted through the filter: namely, because the distance between the potassium ion and the oxygen atoms in the filter is the same as that between the potassium ion and the oxygen atoms in the water molecules surrounding the potassium ion when it is outside the filter. Thus it can slide through the filter unopposed. However, the sodium ion, which is smaller than the potassium ion, can not pass through the channel. This is because it does not fit between the oxygen atoms in the filter and therefore remains in the water solution. The ability of the channel to strip the potassium ion of its water and allow it to pass at no cost in energy is a kind of selective catalysed ion transport.

The cell must also be able to control the opening and closing of ion channels. MacKinnon has shown that this is achieved by a gate at the bottom of the channel which opened and closed a molecular "sensor". This sensor is situated close to the gate. Certain sensors react to certain signals, e.g. an increase in the concentration of calcium ions, an electric voltage over the cell membrane or binding of a signal molecule of some kind. By connecting different sensors to ion channels, nature has created channels that respond to a large number of different signals.

Fig 4. The ion channel permits passage of potassium ions but not sodium ions. The oxygen atoms of the ion filter form an environment very similar to the water environment outside the filter. The cell may also control opening and closing of the channel.

High resolution image (jpeg 137 kB) »

OUTSIDE THE ION FILTER (A) Outside the cell membrane the ions are bound to water molecules with certain distances to the oxygen atoms of the water.

High resolution image (jpeg 121 kB)  »

INSIDE THE ION FILTER (B) For the potassium ions the distance to the oxygen atoms in the ion filter is the same as in water.

The sodium ions, which are smaller, do not fit in between the oxygen atoms in the filter. This prevents them from entering the channel.

Understanding diseases
Membrane channels are a precondition for all living matter. For this reason, increased understanding of their function constitutes an important basis for understanding many disease states. Dehydration of various types, and sensitivity to heat, are connected with the efficancy of the aquaporins. The European heat waves of recent years, for example, resulted in many deaths where the cause has sometimes been connected to problems in maintaining the body-fluid balance. In these processes the aquaporins are of crucial importance.

Disturbances in ion channel function can lead to serious diseases of the nervous system as well as the muscles, e.g. the heart. This makes the ion channels important drug targets for the pharmaceutical industry."

"Illustrations: Typoform

Links and further reading »

---

The Laureates
Peter Agre Departement of Biological Chemistry 420 Physiology Building Johns Hopkins University School of Medicine 725 North Wolfe Street Baltimore Maryland 21205 USA	US citizen. Born 1949 (54 years) in Northfield, Minnesota, USA. B.A. at Augsburg College, Minneapolis, chemistry major, 1970. M.D. at Johns Hopkins University School of Medicine in Baltimore, 1974. Since 1993, Professor of Biological Chemistry and Professor of Medicine at Johns Hopkins School of Medicine.
Roderick MacKinnon Howard Hughes Medical Institute Laboratory of Molecular Neurobiology and Biophysics Rockefeller University 1230 York Avenue, New York, New York 10021 USA	US citizen. Born 1956 (47 years). Grew up in Burlington outside Boston, USA. B.A. at Brandeis University, Boston, 1978. M.D. at Tufts Medical School in Boston, 1982. Since 1996, Professor of Molecular Neurobiology and Biophysics at The Rockefeller University in New York."

http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.html

I hope you've been liking all this information. Use this information to learn how to keep your body more hydrated. Post your questions and comments on this blog. I'll answer them and get other opinions during my next interviews with hydrations experts.

-Joshua

"During the past ten years, water channels have developed into a highly topical research field. The aquaporins have proved to be a large protein family. They exist in bacteria, plants and animals. In the human body alone, at least eleven different variants have been found.

The function of these proteins has now been mapped in bacteria and in plants and animals, with focus on their physiological role. In humans, the water channels play an important role in, among other organs, the kidneys.

The kidney is an ingenious apparatus for removing substances the body wishes to dispose of. In its windings (termed glomeruli), which function as a sieve, water, ions and other small molecules leave the blood as 'primary' urine. Over 24 hours, about 170 litres of primary urine is produced. Most of this is reabsorbed with a series of cunning mechanisms so that finally about one litre of urine a day leaves the body.

From the glomeruli, primary urine is passed on through a winding tube where about 70% of the water is reabsorbed to the blood by the aquaporin AQP1. At the end of the tube, another 10% of water is reabsorbed with a similar aquaporin, AQP2. Apart from this, sodium, potassium and chloride ions are also reabsorbed into the blood. Antidiuretic hormone (vasopressin) stimulates the transport of AQP2 to cell membranes in the tube walls and hence increases the water resorption from the urine. People with a deficiency of this hormone might be affected by the disease diabetes insipidus with a daily urine output of 10-15 litres."

http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.html

More coming soon…

-Joshua

"The hunt for the water channels
As early as the middle of the nineteenth century it was understood that there must be openings in the cell membrane to permit a flow of water and salts. In the middle of the 1950s it was discovered that water can be rapidly transported into and out of cells through pores that admit water molecules only. During the next 30 years this was studied in detail and the conclusion was that there must be some type of selective filter that prevents ions from passing through the membrane while water molecules, which are uncharged, flow freely. Thousands of millions of water molecules per second pass through one single channel!

Although this was known, it was not until 1992 that anybody was able to identify what this molecular machinery really looked like; that is, to identify what protein or proteins formed the actual channel. In the mid-1980s Peter Agre studied various membrane proteins from the red blood cells. He also found one of these in the kidney. Having determined both its peptide sequence and the corresponding DNA sequence, he realised that this must be the protein that so many had sought before him: the cellular water channel.

Agre tested his hypothesis in a simple experiment (fig. 2) where he compared cells which contained the protein in question with cells which did not have it. When the cells were placed in a water solution, those that had the protein in their membranes absorbed water by osmosis and swelled up while those that lacked the protein were not affected at all. Agre also ran trials with artificial cells, termed liposomes, which are a type of soap bubble surrounded on the outside and the inside by water. He found that the liposomes became permeable to water if the protein was planted in their membranes.

What is osmosis? The liquid pressure in plant and animal cells is maintained through osmosis. In osmosis, small molecules (such as water) pass through a semi-permeable membrane. If the membrane does not admit macromolecules or salts that are in higher concentrations on one side of the membrane, the small molecules (water) will cross to this side, attempting to "dilute" the substance that cannot pass through the membrane. The osmotic pressure thus arising is the reason why cells are often swollen and stiff, in a flower stalk, for example.

 

High resolution image (jpeg 165 kB) »

Fig 2. Peter Agre's experiment with cells containing or lacking aquaporin. The aquaporin is necessary for making the cell absorb water and swell.

Peter Agre also knew that mercury ions prevent cells from taking up and releasing water, and he showed that water transport through his new protein was prevented in the same way by mercury. This made him even more sure of that he had discovered what was actually the water channel . Agre named the protein aquaporin, "water pore".

How does the water channel work? A question of form and function
In 2000, together with other research teams, Agre reported the first high-resolution images of the three-dimensional structure of the aquaporin. With these data, it was possible to map in detail how a water channel functions. How is it that it only admits water molecules and not other molecules or ions? The membrane is, for instance, not allowed to leak protons. This is crucial because the difference in proton concentration between the inside and the outside of the cell is the basis of the cellular energy-storage system.

Selectivity is a central property of the channel. Water molecules worm their way through the narrow channel by orienting themselves in the local electrical field formed by the atoms of the channel wall. Protons (or rather oxonium ions, H₃O⁺) are stopped on the way and rejected because of their positive charges.

High resolution image (jpeg 173 kB) »

Animations »

Fig 3. Passage of water molecules through the aquaporin AQP1. Because of the positive charge at the center of the channel, positively charged ions such as H3O+, are deflected. This prevents proton leakage through the channel."

http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.html

The animation which is linked above is very helpful to understand what the significance of aquaporin water channels is. Check it out and let me know what you think.

-Joshua

"8 October 2003

All living matter is made up of cells. A single human being has as many as the stars in a galaxy, about one hundred thousand million. The various cells – e.g. muscle cells, kidney cells and nerve cells – act together in an intricate system in each one of us. Through pioneering discoveries concerning the water and ion channels of cells, this year's Nobel Laureates Peter Agre and Roderick MacKinnon, have contributed to fundamental chemical knowledge on how cells function. They have opened our eyes to a fantastic family of molecular machines: channels, gates and valves all of which are needed for the cell to function."

"To maintain even pressure in the cells it is important that water can pass through the cell wall. This has been known for a long time. The appearance and function of these pores, remained for a long time as one of the classical unsolved problems of biochemistry. It was not until around 1990 that Peter Agre discovered the first water channel. Like so much else in the living cell, it was all about a protein.

Water molecules are not the only entities that pass into and out of the cell. For thousands of millions of cells to be able to function as something other than one large lump, coordination is required. Thus communication between the cells is necessary. The signals sent in and between cells consist of ions or small molecules. These start cascades of chemical reactions that cause our muscles to tense, our eyes to water – indeed, that control all our bodily functions. The signals in our brains also involve such chemical reactions. When we stub a toe this starts a signal moving up towards the brain. Along a chain of nerve cells, through interaction between chemical signals and ion currents, information is conveyed from cell to cell like a baton in a relay race.

It was in 1998 that Roderick MacKinnon succeeded for the first time in showing what ion channels look like at atomic level – an achievement which, together with Agre's discovery of water channels, opened up entirely new research areas in biochemistry and biology.

The medical consequences of Agre's and MacKinnon's discoveries are also important. A number of diseases can be attributed to poor functioning in the water and ion channels of the human body. With the help of fundamental knowledge of what they look like and how they work, there are now new possibilities for developing new and more effective pharmaceuticals.

High resolution image (jpeg 210 kB) »

Fig 1. The dividing wall between the cell and the outside world – including other cells – is far from being an impervious shell. On the contrary, it is perforated by various channels. Many of these are specially adapted to one specific ion or molecule and do not permit any other type to pass. Here to the left we see a water channel and to the right an ion channel."

http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.html

This is one of the major breakthroughs in health research in recent years - and it's very misunderstood. More of this is coming soon to this blog as I hope to bring this to the understanding of as many people as possible - please ask your questions about it by commenting on this blog.

-Joshua