Remarkable Minerals - Potassium and Sodium
Today you cannot afford not to know the information this article has for you. It is a matter of life and death. Taking the proper minerals and knowing why is a must for vitality. Cancer cells are found to die in potassium solutions. Potassium improves blood circulation.
Excessive salt intake create a loss of potassium reserves. Lung disease and chest infections are improved by taking high doses of calcium, potassium and sodium. Olives are one of the highest food in potassium and can help nourish the nerves, brain and heart. Potassium is the mineral spark plug that enhances the entire bodys’ cellular healing. Raw food dishes with foods high in potassium are best. Potassium plus phosphorous are a winning combination of minerals that get oxygen to the brain and increase mental functioning. Low levels of potassium can cause irritability.
Potassium is a mineral that should be included in any detox program. The heart uses potassium to keep its muscle strong and in combination with iron brings oxygen to the heart and helps circulate clean ,rich, blood to the rest of the body. The foods highest in potassium are dandelion greens, almonds, raisin, collard, black currants, potato, radish, peas, barley, dates and figs.
Sodium is a strong ingredient in producing a healthy lymphatic system. Sodium must be taken in its organic form such as sea salt. Sodium plays a role in curing lung diseases because it helps remove carbon dioxide from the lungs. Liquid minerals combined with vitamin nutrients are the antidote to the world of the busy. Sodium helps balance magnesium. The main influence sodium has in the body is preventing hardening of the arteries.
You are your own best friend. You can chose to allow knowledge to empower you to heal thyself and thrive. Sodium levels are responsible for the production of saliva which is the first step in digestive enzyme action Skin, hair and eyes are dependent upon the mineral sodium for beauty, clarity and brilliance. Don’t put your lamp under the table shine with your natural power and understand how to consciously chose how to fuel your body intelligently.
Carbohydrates need sodium to process the dreaded good and bad carbohydrate.
These are a list of sodium rich foods ,nuts like cashews, sesame seeds, kumquat, prunes, brusell sprouts, honeydew melon, mango, wheat bran, artichoke , chickpea, cauliflower, onion, coconut, beetroot, garlic and cabbage. Lower levels of sodium but still high in sodium foods are cucumbers, rice, endive, red bean, and cayenne.
Making it your business to understand that the blood needs sodium mineral and 16 other minerals makes it easy to understand it is time right now to act and make sure everyday you are consciously supplying your body with its needs and amazingly enough you will see your body give you what you want.
What about Potassium?
Information on potassium
When you read about potassium and senate document report 264 you’ll life should be changed forever. You’re going to discover that the biggest fallacy most people aren’t aware of is that if we eat a balanced diet, (the four food groups), we get all the nutrients we need to stay healthy and live a long life. The truth is, this has been a matter of public record for the past 60 years. Fact is that our farming soils are severely depleted of these so important minerals such as potassium.
Without adequate mineral intake whether through supplements or certain foods the vitamins our bodies take in are worthless. We need this important mineral as it assists in muscle contraction and in maintaining fluid and electrolyte balance in body cells. Various surveys would have us believe that we get adequate amounts of daily intake but in truth how’s that possible according to the senate document.
We’re taught that potassium rich food does the trick but in reality that really can’t be so. Fruits and vegetables are mostly depleted of nutrients – yes they still look good in the stores for sure. A little fancy treatment makes good marketing sense for the venders but not for us. As we contemplate the issues it makes us really wonder who’s needs are being met with so many conflicting reports.
The giant supermarkets aren’t concerned about our nutrition; it’s the cash register that dictates the bottom line. Plant foods are harvested before they’ve even ripened; many are gas retarded from ripening, trucked across the United States, and then gas ripened. By the time the food gets to our dinner tables there’s little or no nutrition left. But they sure look good.
No longer can we rely on a “balanced” diet with merely so many calories or certain vitamins or fixed proportions of starches, proteins and carbohydrates. We know for certain that our diets must have a score of minerals. And potassium along with many others just isn’t there.
Most Athletes Do Not Need to Replace Potassium
Many sports drinks advertise that they contain potassium, but potassium deficiency is not common in athletes unless they are trying to control weight by vomiting.
A few years ago, one of the best female long-distance runners in the country came to me to find a cause for her sudden drop in performance. All tests I ordered were normal except for a low blood level of potassium. The most common cause of potassium deficiency is vomiting, but she repeatedly denied doing this. I then requested that she collect her urine for one day, and the laboratory reported that it contained three times as much potassium as normal. This proved that she was bulimic. To control her weight, she was sticking her finger down her throat and making herself throw up. After she was able to accept the diagnosis, she got help, stopped vomiting and went on to win several long distance running titles.
The kidneys and sweat glands conserve potassium so effectively in response to low body levels that potassium deficiency rarely occurs in healthy athletes. Even with prolonged exercise in very hot weather, potassium needs can be met by eating a normal diet because potassium is found in virtually all foods except refined sugar. On the other hand, potassium deficiency can be caused by drugs, such as diuretics and corticosteroids. It can also be caused by diarrhea or repeated vomiting. With diarrhea, potassium is lost in the stool. With vomiting, potassium is lost in the urine. In both athletes and non-athletes, the most common cause of low potassium blood levels and high potassium urine levels is vomiting.
Potassium and Its Benefits to the Human Body
Potassium is a mineral that serves a variety of purposes within the body. Despite its importance to so many of the body’s functions and systems, most people do not consume the standard recommended daily levels of this essential mineral. This is unfortunate as long-term deficiency can contribute to and even directly cause a variety of health problems and complications not only to the body but to one’s lifestyle as well.
Helping to regulate the body’s fluid levels is one of the mineral potassium’s greatest functions. Not only that but it also has a great part in regulating the blood pressure. It also helps to keep the heart thumping steadily and regularly and is also essential to the nervous system. Potassium works to promote the proper functioning of the tissue that makes up the nervous system. It also serves to enhance muscle control plus the growth and health of cells particularly through its importance in waste product removal. This mineral is also vital to the kidneys in their waste removal tasks. Potassium also plays an important role to mental function as well as to physical processes. It helps to promote efficient cognitive functioning by playing a significant role in getting oxygen to the brain.
Failing to meet the standard recommended daily intake levels can lead to a variety of negative consequences for both physical well being and mental health. Physical symptoms can include muscular cramps and twitching, muscular weakness, even actual muscle damage, poor reflexes, fatigue, fragile bones, irregular heartbeat and other cardiovascular irregularities, kidney failure, lung failure, and cardiac arrest. Mental symptoms can include nervous disorders of various types, anorexia, insomnia, a slowdown of cognitive processes, and depression.
There are certain health situations that can make a person more susceptible to suffering from a deficiency of potassium. These include alcoholism, health conditions requiring the use of certain types of diuretics, periods of high stress and illnesses or conditions that result in extended periods of diarrhea and vomiting. Some situations of our own making can contribute to potassium deficiency. These include excessive caffeine intake and a diet made up of mostly processed foods. Consuming excessive amount of salt daily can also attribute to the decrease of potassium in the human body.
Our bodies are complex systems in which there is a delicate chemical balance that keeps everything functioning as it should. Disruptions to the system are going to have consequences with some being more severe than others. Some of these consequences can take the form of disease or irreversible damage. Prevention is always better than trying to cure illness or repair damage. One of the most important parts of prevention is good nutrition. Making sure that you regularly consume the standard recommended daily intake levels of the vitamins, mineral and other nutrients your body needs is the first vital step in keeping a healthy physic and mind.
But because of today’s lifestyle and diet, it is very hard therefore to intake the proper daily amount of potassium necessary for a normal life. For this concern, nutritional supplements are the solution. They offer an efficient and reliable means of meeting not only our daily potassium needs but also other daily dietary requirements need by the system. Because the balance of nutrients is so important to achieving the optimum standards of performance and health, you may want to consider setting up a consultation with either a licensed nutritionist or your health care provider to create a personalized supplement plan; one that will be best suited to your individual dietary need and health goals.
Potassium, Deficiency and Potassium Rich Food
Potassium represents 5% percent of the total mineral content of a human body, even though only about one litre is found in the body at a time. Potassium is found in our bodies both inside and outside cells and is a very important mineral required every day to stay healthy. More than 98% of the body’s potassium is intracellular. The body easily absorbs potassium, but nearly 90% of it is excreted through the kidneys and bowels. Thus, potassium is a natural diuretic and is important for the elimination of body wastes, such as water and sodium.
Potassium is a primary electrolyte, it is a great alkalizer, and important for maintaining pH and water balance.
Benefits of potassium:
1. Along with other minerals such as sodium, chloride and calcium, potassium helps in normal cellular function, such as transmission of nerve impulses, digestion, healthy muscle contractions, proper cardiovascular functioning (heartbeat irregularities are normally a sign of potassium deficiency), and helping the body to convert glucose into glycogen (the body’s stored form of energy).
2. Potassium helps promote healthy cardiovascular health. It is strongly believed that potassium has the ability to pump sodium out of the body’s cells and reduce body fluid.
3. Potassium, along with sodium, helps to regulate blood pressure. Increasing potassium in the diet may protect against hypertension in people who are sensitive to high levels of sodium.
4. Potassium also affects blood vessel tone as well as the way blood vessels react to the flowing hormones, thus affecting pressure within blood vessels.
5. Potassium therapeutically assists in the treatment of alcoholism, acne, alleviating allergies, promoting the early healing of burns.
6. It also helps with problems such as congestive heart failure, chronic fatigue syndrome or kidney stones.
7. Potassium plays a vital role in cellular integrity by regulating the transfer of nutrients into the cell.
8. Potassium also attracts oxygen to tissues, helps correct positioning of vital organs. Potassium deficiency indicates that probably albumin, sugar, sodium, and chlorine are also in short supply or not being properly absorbed.
9. Potassium helps proper functioning of the adrenal glands. It helps support healthy sugar balance in the body.
Deficiency of potassium –
The kidneys excrete excess potassium from the body, and deficiencies are rarely found in people on a normal balanced diet. A deficiency may result in fatigue, cramping legs, muscle weakness, sluggish reflexes, acne, dry skin, mood swings and irregular heartbeat.
A shortage of potassium in body may cause a fatal condition known as hypokalemia, resulting from diarrhoea, increased diuresis and vomiting. Hypokalemia can occur in people with a chronic disease or due to ageing process. Deficiency symptoms include muscle weakness, ECG abnormalities, decreased reflex response, congestive heart failure, cardiac arrhythmia and respiratory paralysis.
If the fluid and electrolyte balance is not restored, the risk of heart failure increases.
Potassium deficiency increases acid levels in the body, lowers the natural pH balance, causes problems with the formation of connective tissue. Kidney diseases (such as acute renal failure), diabetes can also cause fluctuations in the levels of potassium. Many medications such as diuretics, cortisone, prolonged use of aspirin, and laxatives also cause depletion of potassium.
Dietary sources of potassium:
Eating a variety of foods that contain potassium is the best way to get the required amount. Individuals who eat a balanced diet do not need potassium supplements. Foods, which are rich sources of potassium include turnips, whole grains, molasses, fish, citrus fruit, apple cider vinegar, bananas, avocados, yoghurt, tomatoes, poultry, oranges, apricots, potatoes (especially their skins), leafy green vegetables such as spinach, lettuce; and meat. One large orange will supply one with 250 mg of potassium, one-eighth of a person’s daily need. Dried apricots contain more potassium than fresh apricots.
Steaming of foods helps to retain nutrients that are lost through other cooking techniques such as boiling (loss of about 50% of potassium content). Steaming results in only a 6% loss of potassium.
Recommended Daily Allowance of potassium:
There is no recommended daily allowance (RDA) for potassium, but it is advised to get between 2,000-3,000 mg per day. The range of intake for children is 780 to 1,600 mg per day.
This is not difficult, and most people meet this requirement on their own through a normal diet. In general, nutritionists recommend reducing salt intake and ensuring adequate supply by increasing the amount of fresh fruit and vegetables in the diet.
If one is into bodybuilding, he must increase the potassium intake, since potassium is needed to maintain muscles in good form, and also because potassium is lost from excessive sweating and urine.
Symptoms of high intake of potassium:
Excessive potassium can be toxic and will affect the heart. This is a problem especially when one is suffering from some problem such as kidney failure. Irregular heart beat and muscle fatigue is sign of toxic potassium levels. In healthy people, the kidneys in the urine excrete excess potassium.
Who requires extra potassium?
People who require potassium supplements include:
- women on oral contraceptives,
- chronic alcoholics or drug abusers,
- smokers
- people undergoing stress
- athletes
- people doing strenuous exertion,
- anyone suffering from any degree of mal-absorption syndrome
- people with eating disorders, especially bulimia and anorexia..
Potassium - One Great Reason to Eat Raw Foods
In this article, I am going to discuss a very essential mineral, which also happens to be an electrolyte: Potassium. This essential mineral was used in an experiment to keep a live chicken heart alive and beating for 30 years! (The janitor bumped it, and thus ended the experiment.) Imagine, only potassium was used to keep the heart beating, and alive for 30 years! In this day and age, compared to a less “civilized” time, many have a lack of potassium, and a huge increase in inhibiting factors of absorption: sodium and sugar. Today I will be discussing many of the benefits of potassium and why you should get it from raw foods, some of the best sources, as well as the deficiency symptoms of not getting enough of this vital nutrient.
Potassium is to your soft tissues, what calcium is to your bones! This wonderful mineral cleans arteries, and promotes youthful skin. It has been found to be associated with lower blood pressure levels, proper digestive & nervous system function, reduced risk of stroke, keeping the heart healthy, decreasing kidney stones, critical for muscle contraction, helping in cases of acne. Some enzymes cannot function without potassium being present, such as the enzyme pyruvate kinase, which helps to digest carbohydrates. Potassium helps to keep the proper water balance in our cells. Need I go on? For more benefits check out my chart directory. The therapeutic applications, as well as the bodily parts affected, and bodily parts facilitated sections in the chart on my website give more info on the benefits of this vital mineral.
The raw food sources are by far the best way to get what you need, as you avoid bad reactions to potassium supplements. Raw foods also supply much of what is needed to absorb the potassium, since most of the sources rich in potassium, are also rich in the enhancing nutrients! Some of the raw foods most rich in potassium are: apricots, avocado, bananas, broccoli, brussel sprouts, buckwheat, cantaloupe, dates, dried fruits, legumes, lima beans, nuts, parsley, peaches, sunflower seeds, sesame seeds, soybeans, spinach, tomato juice, wheat germ. For those who like juicing, good news! One cup of carrot juice is loaded with potassium. One of the most well known raw food sources are apples, and apple cider vinegar. The raw food sources I just listed are not listed in the order of potassium value; to ascertain this, you can visit my website for free info on exactly what foods give how much potassium. Just check out the chart directory-a look at the numbers shows the superiority of the plant sources versus animal sources.
According to Drs. Jane Higdon and Victoria J. Drake of the Linus Pauling Institute at Oregon State University, adults need 4,700 mg of potassium daily. Multivitamins do not generally include potassium, and if they do, not more than 99 mg are in the daily dose, according to the Linus Pauling Institute. I will give you an idea of how much raw food you need to eat daily to obtain 4,700 mgs: 2 bananas, 1 orange, 1 avocado, 1/2 green pepper, 2 apples, 3.3 oz spinach, ¾ of a tomato, 1 whole English cucumber unpeeled, ½ cup of almonds, ½ cup sunflower seeds, and ¾ cup carrot juice. These of course can be substituted with other choices. No wonder most people are deficient in potassium! This is why those on a 100 percent raw food diet have no problem getting their needed potassium, and have such youthful looking skin!
The deficiency symptoms are: acne, bloating, constipation and/or abdominal pain, continuous thirst, decreased blood pressure, dry skin, edema, increased cholesterol levels, insomnia, muscle & general weakness, nervousness, respiratory distress, salt retention, skin & hair problems, slow irregular heartbeat, and weak reflexes.
In conclusion, potassium is an excellent nutrient for disease prevention, and a delicious way to obtain good health. If you haven’t already, simply increase your intake of fresh raw foods rich in potassium to get what you need. Your health is your most important asset. Eating plenty of fresh, raw food will help you achieve optimum health.
Potassium Deficient WLS Patients: Eat Salmon & Grapefruit
Potassium is one of the nutrients gastric bypass patients tend to be deficient. In fact many weight loss surgery patients (WLS) supplement their diet with potassium. By including certain foods in the diet WLS patients can increase their potassium intake.
Of course we have heard all our lives to eat a banana when low on potassium. But did you know there are many foods rich in potassium, which are better tolerated than the banana by most weight loss surgery patients? Foods such as apricots, butternut squash, grapefruit, salmon, halibut and chicken are all potassium powerhouses. By incorporating these foods in our meals after gastric bypass we benefit from flavor, variety and healthful nutrients and perhaps stave-off some of the food boredom we all complain about. In addition, we know WLS patients are at risk of potassium deficiency so why not get some the old fashioned way – delicious home cooked food.
One of my favorite potassium rich recipes includes salmon and grapefruit, ingredients that are available year round and easily digested by the weight loss surgery patient.
Grapefruit-Broiled Salmon
Prep: 20 minutes/ Cook: 10 minutes
This WLS friendly recipe tastes great and is nutrient dense with vitamin C, potassium and dietary fiber from the grapefruit and heat-friendly Omega 3 fatty acids in the salmon. A normal serving of Grapefruit-Broiled Salmon contains about 40% daily value potassium. The salad is good served cold the next day.
Ingredients:
3 grapefruits (or one jar canned grapefruit)
1 red bell pepper, diced
1 celery stalk cut into ¼-inch dice
¼ cup finely chopped red onion
2 teaspoons olive oil
1 teaspoon Dijon mustard
½ teaspoon salt
4 boneless salmon fillets, with skin (6 ounces each)
½ teaspoon dried oregano
¼ teaspoon black pepper
Directions:
1. With a small paring knife, peel the grapefruits. Working over a bowl to catch the juice separate the grapefruit sections from the membranes; reserve any juice that collects in the bowl. Halve the grapefruit sections crosswise and transfer to a salad bowl. Add the bell pepper, celery, oinon, oil, mustard, and ½ teaspoon of the salt. Toss to combine and refrigerate until serving.
2. Preheat the broiler. Place the salmon, skin-side down, on a broiler rack. Sprinkle 3 tablespoons of the reserved grapefruit juice, the oregano, black pepper and remaining ¼ teaspoon salt over the salmon. Broil 6 inches from the heat for 8 minutes or until just cooked through. Serve the salmon with the grapefruit salad.
A Constipation Remedy Using Potassium and Prunes
Potassium and prunes are a natural constipation remedy that you can quickly use to help you get constipation relief.
Potassium is needed in your colon walls to insure that peristaltic action occurs. Without potassium, colon walls are weak and unable to respond and contract properly when fecal matter needs to be move.
Potassium in your colon wall tissues brings in more oxygen, which is required for good cell function and elimination of toxins. In addition, potassium creates an alkaline environment inside and outside the cell, which help protect cell walls from bacteria, fungus, and other pathogens.
Potassium is a powerful source when it comes to cleaning, feeding and building your colon walls. Removing the thin layer of buildup – harden mucus, dried fecal matter, waste derby, heavy metals - against your colon wall can be accomplished by eating those foods that are high in potassium.
Excess buildup on your colon walls of fecal matter and toxins is a cause of continual constipation. This build up prevents your colon walls from functioning properly.
Potassium is necessary for reducing anxiety and depression. These conditions can affect peristaltic movements of your colon. Lack of it causes muscles and organs to sag and lack tone.
Potassium, also, draws water out of the body. So when potassium is in your colon it attracts water and pulls it into the fecal matter. This makes your fecal matter softer and easier to move along the colon.
To get more potassium into your diet make a constipation remedy drink by,
Pouring hot water over dried prunes and waiting 10 minutes. Then eat the prunes and drink the juice Do this on an empty stomach in the morning.
The high concentration of potassium and vitamin A, in prunes, stimulates enzymatic processes. These processes melt down fecal wall wastes and dissolve blockages. They also activate peristaltic action to move this waste out through your rectum.
The foods to eat that are high in potassium are:
Kale, cabbage, yellow tomatoes, spinach, carrots, broccoli, cucumbers, cauliflower, alfalfa sprouts, goat milk, sesame seeds, wheat germ brewers yeast, flax seed, grapes, green peppers, pineapple, beets, potatoes with skin Blackstrap molasses
If you have any kidney disease, do not take potassium supplements unless directed by your doctor. If you are pregnant, take potassium only under a doctor’s direction.
If you are on any type of drugs, do not take potassium unless directed by your doctor.
When you have constipation it is best to take potassium supplement. Once you have your constipation eliminated back off on the potassium you are taking and depend on your potassium dose from the foods you eat.
My recommended Potassium dose is 1000 – 3000 mg each day taken with meals.
Interactions of phospholipids with the potassium channel KcsA
ABSTRACT The potassium channel KcsA from Streptomyces lividans has been reconstituted into bilayers of phosphatidylcholines and fluorescence spectroscopy has been used to characterize the response of KcsA to changes in bilayer thickness. The Trp residues in KcsA form two bands, one on each side of the membrane. Trp fluorescence emission spectra and the proportion of the Trp fluorescence intensity quenchable by I - hardly vary in the lipid chain length range Cl 0 to C24, suggesting efficient hydrophobic matching between KcsA and the lipid bilayer over this range. Measurements of fluorescence quenching for KcsA reconstituted into mixtures of brominated and nonbrominated phospholipids have been analyzed to give binding constants of lipids for KcsA, relative to that for dioleoylphosphatidylcholine (di(C18:1)PC). Relative lipid binding constants increase by only a factor of three with increasing chain length from Cl 0 to C22 with a decrease from C22 to C24. Strongest binding to di(C22:1)PC corresponds to a state in which the side chains of the lipid-exposed Trp residues are likely to be located within the hydrocarbon core of the lipid bilayer. It is suggested that matching of KcsA to thinner bilayers than di(C24:1)PC is achieved by tilting of the transmembrane a-helices in KcsA. Measurements of fluorescence quenching of KcsA in bilayers of brominated phospholipids as a function of phospholipid chain length suggest that in the chain length range Cl 4 to Cl 8 the Trp residues move further away from the center of the lipid bilayer with increasing chain length, which can be partly explained by a decrease in helix tilt angle with increasing bilayer thickness. In the chain length range C18 to C24 it is suggested that the Trp residues become more buried within the hydrocarbon core of the bilayer.
Intrinsic membrane proteins must have co-evolved with the lipid component of the membrane to give optimal function, within the constraints imposed by the role of lipids in the general physiology of the cell and by the requirements of the biosynthetic machinery for translation and insertion of proteins into membranes. The rules describing the relationship between the lipid and protein components of the membrane are still being defined. One important property of the membrane is its hydrophobic thickness, defined as the separation between the glycerol backbone regions of the two leaflets making up the bilayer. The cost of exposing hydrophobic groups to water is high, so that the hydrophobic lengths of protein a-helices spanning the membrane would be expected to be equal to the hydrophobic thickness of the bilayer around the helices; this could be equal to the bulk thickness of the lipid bilayer in the absence of protein, or the bilayer could be distorted around the protein to give a thicker or thinner bilaver.
The thickness of a lipid bilayer in the liquid crystalline phase will be constantly fluctuating as a consequence of the molecular motion of the lipids. This is shown, for example, by the width of the Gaussian distributions representing the positions of groups in a liquid crystalline bilayer (Wiener and White, 1992). Molecular dynamics simulations also emphasize the roughness of the membrane surface resulting from lipid motions with occasional lipid molecules protruding from the surface of the bilayer (Tieleman et al., 1997). Further, biological membranes contain a wide variety of lipid species with different fatty acyl chains so that lateral diffusion of lipid molecules within the plane of the membrane will result in fluctuating local thicknesses for the membrane.
Activities of a number of membrane proteins are sensitive to the thickness of the lipid bilayer, with the optimal thickness usually corresponding to that of a bilayer of dioleoylphosphatidylcholine (di(C18:1)PC) (Caffrey and Feigenson, 1981; Lee, 1998). One mechanism to reduce the effect of fluctuating bilayer thickness on the function of a membrane protein could be to reduce bilayer fluctuations in the vicinity of the protein. Indeed, the mobility of lipid molecules is reduced when they interact with the relatively immobile surface of a membrane protein, as shown by the presence of an “immobile” fraction of lipid in electron spin resonance (ESR) studies with spin-labeled lipid molecules (for example, see East et al., 1985; Marsh, 1995). Anchoring the protein firmly into the lipid bilayer could also reduce effects of changing bilayer thickness. It has been suggested that aromatic residues at the ends of transmembrane a-helices could achieve this by acting as “floats” at the interface; aromatic residues, particularly Trp, are found preferentially at the ends of transmembrane a-helices.
The exact location of Trp residues at the ends of transmembrane a-helices relative to the surrounding lipid bilayer is uncertain. Small water soluble analogues of Trp have been shown to bind in the glycerol backbone and lipid headgroup region of a lipid bilayer, stabilized partly by location of the aromatic ring in the electrostatically complex environment provided by this region of the bilayer and partly by exclusion of the flat, rigid ring system from the hydrocarbon core of the bilayer for entropic reasons (Yau et al., 1998). In contrast, aromatic residues in small peptides binding to the surfaces of lipid bilayers have been shown to penetrate into the hydrocarbon core region of the bilayer (Jacobs and White, 1989; Brown and Huestis, 1993). In the crystal structure of the bacterial photosynthetic reaction center the majority of the Trp residues are found near the ends of transmembrane a-helices with detergent molecules covering some of the Trp residues but not others (Roth et al., 1991). It is also likely that only some of the Trp residues in the photosynthetic reaction center will be located in the hydrocarbon core of a lipid bilayer. The hydrophobic thickness of a bilayer of a typical lipid such as di(C18:1)PC is 30 A, which is insufficient to cover all of the Trp residues in the photosynthetic reaction center, so that some Trp residues would necessarily be located in the headgroup regions of the bilayer. In the potassium channel KcsA of Streptomyces lividans (Doyle et al., 1998; Zhou et al., 2001) the distribution of Trp residues is particularly clear (Fig. 1). The Trp residues form bands on the two sides of the membrane with the rings of the Trp residues being almost parallel to the surface of the membrane. On the periplasmic side of the membrane, Tyr residues also form a clear band “above” the band formed by the Trp residues. Two partial lipid molecules are seen in the x-ray structure, one modeled as nonan-1-ol and the other as a diacylglycerol with one C14 and one C9 chain (Zhou et al., 2001). As shown in Fig. 1, the diacylglycerol molecule is located close to Trp-87 with the Trp ring system just below the glycerol backbone of the diacylglycerol.
Brownian dynamics simulations of the recognition of the scorpion toxin maurotoxin with the voltage-gated potassium ion channels
ABSTRACT The recognition of the scorpion toxin maurotoxin (MTX) by the voltage-gated potassium (Kv1) channels, Kv1.1, Kv1.2, and Kv1.3, has been studied by means of Brownian dynamics (BD) simulations. All of the 35 available structures of MTX in the Protein Data Bank (http://www.rcsb.org/pdb) determined by nuclear magnetic resonance were considered during the simulations, which indicated that the conformation of MTX significantly affected both the recognition and the binding between MTX and the Kv1 channels. Comparing the top five highest-frequency structures of MTX binding to the Kv1 channels, we found that the Kv1.2 channel, with the highest docking frequencies and the lowest electrostatic interaction energies, was the most favorable for MTX binding, whereas Kv1.1 was intermediate, and Kv1 .3 was the least favorable one. Among the 35 structures of MTX, the 10th structure docked into the binding site of the Kv1.2 channel with the highest probability and the most favorable electrostatic interactions. From the MTX-Kv1.2 binding model, we identified the critical residues for the recognition of these two proteins through triplet contact analyses. MTX locates around the extracellular mouth of the Kv1 channels, making contacts with its p-sheets. Lys23, a conserved amino acid in the scorpion toxins, protrudes into the pore of the Kv1.2 channel and forms two hydrogen bonds with the conserved residues Gly401 (D) and Tyr400(C) and one hydrophobic contact with Gly401 (C) of the Kv1.2 channel. The critical triplet contacts for recognition between MTX and the Kv1.2 channel are Lys23(MTX)-Asp402(C)(Kv1), Lys27(MTX)-Asp378(D)(Kv1), and Lys30(MTX)-Asp402(A)(Kv1). In addition, six hydrogen-bonding interactions are formed between residues Lys23, Lys27, Lys30, and Tyr32 of MTX and residues Gly401, Tyr400, Asp402, Asp378, and Thr406 of Kv1.2. Many of them are formed by side chains of residues of MTX and backbone atoms of the Kvl.2 channel. Five hydrophobic contacts exist between residues Pro20, Lys23, Lys30 and Tyr32 of MTX and residues Asp402, Va1404, Gly401, and Arg377 of the Kv1.2 channel. The simulation results are in agreement with the previous molecular biology experiments and explain the binding phenomena between MTX and Kvi channels at the molecular level. The consistency between the results of the BD simulations and the experimental data indicated that our three-dimensional model of the MTX-Kv1.2 channel complex is reasonable and can be used in additional biological studies, such as rational design of novel therapeutic agents blocking the voltage-gated channels and in mutagenesis studies in both the toxins and the Kv1 channels. In particular, both the BD simulations and the molecular mechanics refinements indicate that residue Asp378 of the Kv1.2 channel is critical for its recognition and binding functionality toward MTX. This phenomenon has not been appreciated in the previous mutagenesis experiments, indicating this might be a new clue for additional functional study of Kvi channels.
During the last decade, interest has increased tremendously in the rational design of drugs acting on potassium channels (Hoshi et al., 1990; Goldstein et al., 1994; Legros et al., 2000; Carlier et al., 2001). Several excellent reviews have dealt with the structural features that underlie particular biophysical and pharmacological properties of potassium channels. Recent research (Kaczorowski et al., 1999) has focused on the Kv1 channels and indicated that Kv1 family members may also constitute novel therapeutic targets. Voltage-gated (Kv1) potassium channels are widely distributed in the central and peripheral nervous system. Lacking this channel will result in some diseases such as spontaneous epileptic seizures (Smart et al., 1998), learning deficiencies (Meiri et al., 1997), and pathophysiology of episodic ataxia/myokymia and neurotransmitter release (Brandt and Strupp, 1997). Therefore, it is very important to study the drugs that act on these Kv1 channel proteins. At present, a variety of experimental strategies have defined functional domains within these Kv1 channel proteins (Aiyar et al., 1995), and some thermodynamic mutant cycle analyses have been used to identify specific amino acid residues in the SS-S6 linker region that are part of the scorpion-toxin receptor site (Aiyar et al., 1995; Doyle et al., 1998; Mackinnon et al., 1998). However, many questions are still unresolved because of experimental difficulties and the lack of significant theoretical guidance. All drugs now marketed that act on ion channels were discovered empirically rather than by molecular insight, and most have been shown to have serious safety and efficacy problems (Goldstein and Colatsky, 1996; Kaczorowski and Garcia, 1999). Therefore, theoretical simulations at the molecular level can be a powerful tool and will help to understand electrophysiological experiments performed on wild-type and mutant channels. Our interest in the mechanism of blockage of Kv1 channels stems from our efforts to design new ion channel blockers, with the eventual aim to develop new drugs for the treatment of diseases affecting both electrically excitable and nonexcitable tissues. In particular, our research is focused on the application of molecular simulation and modeling methods in the rational design of new blocking agents of Kv1 channels.