Walter F. Boron | |
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Born | |
Alma mater | Saint Louis University, Washington University in St. Louis |
Scientific career | |
Institutions | Case Western Reserve University |
Academic advisors | Emile L. Boulpaep, Albert Roos |
Walter F. Boron (born November 18, 1949) [1] is an American scientist and the 72nd president of the American Physiological Society (from 1999 to 2000). [2] He was Secretary-General of the International Union of Physiological Sciences. [3] Additionally, Boron is co-editor, along with Emile L. Boulpaep, of the textbook Medical Physiology and Concise Medical Physiology. He is a former editor-in-chief of two leading physiology journals, Physiological Reviews and Physiology .
Boron obtained his AB degree in chemistry, summa cum laude from Saint Louis University in 1971. He then joined the Medical Scientist Training Program at Washington University School of Medicine, where he received his M.D. and Ph.D. degrees in 1977 under the mentorship of Albert Roos. [4] [5] During this time, Boron also collaborated with Paul De Weer and John M. Russell . Boron joined Yale University as a postdoctoral fellow with Emile L. Boulpaep in the Department of Physiology, from 1978 to 1980.
Boron is the David N. and Inez Myers/Antonio Scarpa Professor and Chair of the Department of Physiology and Biophysics at Case Western Reserve University. [6] He is also Professor of Medicine and Professor of Biochemistry. Since 2016, he has been Executive Director of PhD programs at the School of Medicine. He briefly served as Interim Chair of the Department of Biochemistry (from 2017 to 2018). Previously, he was a member of the faculty of Yale University (from 1989-2007), serving three 3-year terms as Chair of the Department of Cellular and Moleculary Physiology from 1989 through 1998.
Boron's lifelong research interest has been pH (acid-base) homeostasis. With his colleagues, he was the first to demonstrate cell-pH regulation, developed the first mathematical model of cell-pH regulation, discovered several sodium-coupled/bicarbonate cotransporters (the NBCs), was the first to clone the DNA encoding an NBC, discovered the sensing of molecular carbon dioxide and bicarbonate, and introduced several paradigms for studying cellular acid-base physiology. His laboratory has elucidated the mechanisms and control of acid-base transport in kidney tubules, and pH regulation in neurons and glial cells from the central nervous system. [7] [8] discovered and cloned several bicarbonate transporters, [9] elucidated the sensing of molecular carbon dioxide and bicarbonate, [10] [2] and introduced several experimental paradigms for studying cellular acid-base physiology. [11] [2]
While studying pH regulation in cells from the stomach, Boron and his colleagues became the first to describe a membrane that does not permit the penetration of carbon dioxide. This result led to the discovery of the first gas channel (a protein channel in a cell membrane that is permeable to a gas), namely aquaporin-1. Boron's group has extended its interest to understanding mechanisms of gas movement through aquaporins, Rh proteins, and other membrane proteins, and the physiological significance of these movements.
Boron was a Searle Scholar from 1981 to 1984. He received the Homer Smith Award from the American Society of Nephrology in 2005, the Sharpey-Schafer Award from The Physiological Society (London) in 2008, and the Palade Gold Medal (shared with William Catterall and Richard Tsien) from Wayne State University in 2010. In 2014, Boron received an honorary doctorate from Aarhus University in Denmark, and was elected to the National Academy of Medicine. He was appointed Distinguished University Professor at Western Reserve University in 2020.
Boron and Marc Pelletier co-founded Aeromics Corporation, which discovered the first high-affinity blocker of an aquaporin water blocker. This drug, which has now passed Phase 1 clinical trials, greatly slows the movement of water into the brain (cerebral edema) in models of stroke in mice and rats, and greatly improves clinical outcome. In addition, Boron, George Farr, and Paul Schlather founded Remsenwood Associates, an umbrella company that has created JanusQ, LLC.
In biology, homeostasis is the state of steady internal, physical, chemical, and social conditions maintained by living systems. This is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance, being kept within certain pre-set limits. Other variables include the pH of extracellular fluid, the concentrations of sodium, potassium, and calcium ions, as well as the blood sugar level, and these need to be regulated despite changes in the environment, diet, or level of activity. Each of these variables is controlled by one or more regulators or homeostatic mechanisms, which together maintain life.
A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the site of the exchange of many substances from the surrounding interstitial fluid, and they convey blood from the smallest branches of the arteries (arterioles) to those of the veins (venules). Other substances which cross capillaries include water, oxygen, carbon dioxide, urea, glucose, uric acid, lactic acid and creatinine. Lymph capillaries connect with larger lymph vessels to drain lymphatic fluid collected in microcirculation.
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek erythros 'red' and kytos 'hollow vessel', with -cyte translated as 'cell' in modern usage), are the most common type of blood cell and the vertebrate's principal means of delivering oxygen (O2) to the body tissues—via blood flow through the circulatory system. RBCs take up oxygen in the lungs, or in fish the gills, and release it into tissues while squeezing through the body's capillaries.
Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands. In humans, the secretin peptide is encoded by the SCT gene.
Diuresis is the excretion of urine, especially when excessive (polyuria). The term collectively denotes the physiologic processes underpinning increased urine production by the kidneys during maintenance of fluid balance.
In cell biology, protein kinase A (PKA) is a family of enzymes whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase. PKA has several functions in the cell, including regulation of glycogen, sugar, and lipid metabolism. It should not be confused with 5'-AMP-activated protein kinase.
Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of a variety of different bacteria, fungi, animal and plant cells contain aquaporins through which water can flow more rapidly into and out of the cell than by diffusing through the phospholipid bilayer. Aquaporins have six membrane-spanning alpha helical domains with both carboxylic and amino terminals on the cytoplasmic side. Two hydrophobic loops contain conserved asparagine-proline-alanine which form a barrel surrounding a central pore-like region that contains additional protein density. Because aquaporins are usually always open and are prevalent in just about every cell type, this leads to a misconception that water readily passes through the cell membrane down its concentration gradient. Water can pass through the cell membrane through simple diffusion because it is a small molecule, and through osmosis, in cases where the concentration of water outside of the cell is greater than that of the inside. However, because water is a polar molecule this process of simple diffusion is relatively slow, and in tissues with high water permeability the majority of water passes through aquaporin.
Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, altitude sickness, periodic paralysis, idiopathic intracranial hypertension, heart failure and to alkalinize urine. It may be used long term for the treatment of open angle glaucoma and short term for acute angle closure glaucoma until surgery can be carried out. It is taken by mouth or injection into a vein. Acetazolamide is a first generation carbonic anhydrase inhibitor and it decreases the ocular fluid and osmolality in the eye to decrease intraocular pressure.
The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in electrolyte and fluid balance through reabsorption and excretion, processes regulated by the hormones aldosterone and vasopressin.
Renal physiology is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.
The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal straight tubule (PST).
In the pacemaking cells of the heart (e.g., the sinoatrial node), the pacemaker potential (also called the pacemaker current) is the slow, positive increase in voltage across the cell's membrane (the membrane potential) that occurs between the end of one action potential and the beginning of the next action potential. This increase in membrane potential is what causes the cell membrane, which typically maintains a resting membrane potential around -65 mV, to reach the threshold potential and consequently fire the next action potential; thus, the pacemaker potential is what drives the self-generated rhythmic firing (automaticity) of pacemaker cells, and the rate of change (i.e., the slope) of the pacemaker potential is what determines the timing of the next action potential and thus the intrinsic firing rate of the cell. In a healthy sinoatrial node (SAN, a complex tissue within the right atrium containing pacemaker cells that normally determine the intrinsic firing rate for the entire heart), the pacemaker potential is the main determinant of the heart rate. Because the pacemaker potential represents the non-contracting time between heart beats (diastole), it is also called the diastolic depolarization. The amount of net inward current required to move the cell membrane potential during the pacemaker phase is extremely small, in the order of few pAs, but this net flux arises from time to time changing contribution of several currents that flow with different voltage and time dependence. Evidence in support of the active presence of K+, Ca2+, Na+ channels and Na+/K+ exchanger during the pacemaker phase have been variously reported in the literature, but several indications point to the “funny”(If) current as one of the most important.(see funny current). There is now substantial evidence that also sarcoplasmic reticulum (SR) Ca2+-transients participate to the generation of the diastolic depolarization via a process involving the Na–Ca exchanger.
Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions of the stomach. They contain an extensive secretory network of canaliculi from which the HCl is secreted by active transport into the stomach. The enzyme hydrogen potassium ATPase (H+/K+ ATPase) is unique to the parietal cells and transports the H+ against a concentration gradient of about 3 million to 1, which is the steepest ion gradient formed in the human body. Parietal cells are primarily regulated via histamine, acetylcholine and gastrin signalling from both central and local modulators.
The sarcolemma also called the myolemma, is the cell membrane surrounding a skeletal muscle fiber or a cardiomyocyte. It consists of a lipid bilayer and a thin outer coat of polysaccharide material (glycocalyx) that contacts the basement membrane. The basement membrane contains numerous thin collagen fibrils and specialized proteins such as laminin that provide a scaffold to which the muscle fiber can adhere. Through transmembrane proteins in the plasma membrane, the actin skeleton inside the cell is connected to the basement membrane and the cell's exterior. At each end of the muscle fiber, the surface layer of the sarcolemma fuses with a tendon fiber, and the tendon fibers, in turn, collect into bundles to form the muscle tendons that adhere to bones.
Band 3 anion transport protein, also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1), is a protein that is encoded by the SLC4A1 gene in humans.
Acid–base homeostasis is the homeostatic regulation of the pH of the body's extracellular fluid (ECF). The proper balance between the acids and bases in the ECF is crucial for the normal physiology of the body—and for cellular metabolism. The pH of the intracellular fluid and the extracellular fluid need to be maintained at a constant level.
In acid base physiology, the Davenport diagram is a graphical tool, developed by Horace W. Davenport, that allows a clinician or investigator to describe blood bicarbonate concentrations and blood pH following a respiratory and/or metabolic acid-base disturbance. The diagram depicts a three-dimensional surface describing all possible states of chemical equilibria between gaseous carbon dioxide, aqueous bicarbonate and aqueous protons at the physiologically complex interface of the alveoli of the lungs and the alveolar capillaries. Although the surface represented in the diagram is experimentally determined, the Davenport diagram is rarely used in the clinical setting, but allows the investigator to envision the effects of physiological changes on blood acid-base chemistry. For clinical use there are two recent innovations: an Acid-Base Diagram which provides Text Descriptions for the abnormalities and a High Altitude Version that provides text descriptions appropriate for the altitude.
Emile Louis Boulpaep is a Belgian physiologist and since 1977 President of the Belgian American Educational Foundation. He is a member of the board of the Francqui Foundation.
Porosomes are cup-shaped supramolecular structures in the cell membranes of eukaryotic cells where secretory vesicles transiently dock in the process of vesicle fusion and secretion. The transient fusion of secretory vesicle membrane at a porosome, base via SNARE proteins, results in the formation of a fusion pore or continuity for the release of intravesicular contents from the cell. After secretion is complete, the fusion pore temporarily formed at the base of the porosome is sealed. Porosomes are few nanometers in size and contain many different types of protein, especially chloride and calcium channels, actin, and SNARE proteins that mediate the docking and fusion of the vesicles with the cell membrane. Once the vesicles have docked with the SNARE proteins, they swell, which increases their internal pressure. They then transiently fuse at the base of the porosome, and these pressurized contents are ejected from the cell. Examination of cells following secretion using electron microscopy, demonstrate increased presence of partially empty vesicles following secretion. This suggested that during the secretory process, only a portion of the vesicular contents are able to exit the cell. This could only be possible if the vesicle were to temporarily establish continuity with the cell plasma membrane, expel a portion of its contents, then detach, reseal, and withdraw into the cytosol (endocytose). In this way, the secretory vesicle could be reused for subsequent rounds of exo-endocytosis, until completely empty of its contents.
The anion exchanger family is a member of the large APC superfamily of secondary carriers. Members of the AE family are generally responsible for the transport of anions across cellular barriers, although their functions may vary. All of them exchange bicarbonate. Characterized protein members of the AE family are found in plants, animals, insects and yeast. Uncharacterized AE homologues may be present in bacteria. Animal AE proteins consist of homodimeric complexes of integral membrane proteins that vary in size from about 900 amino acyl residues to about 1250 residues. Their N-terminal hydrophilic domains may interact with cytoskeletal proteins and therefore play a cell structural role. Some of the currently characterized members of the AE family can be found in the Transporter Classification Database.
72nd APS President (1999-2000)