Na+K+-ATPase: Discovery, Functions and Regulation


Book Description

Sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) is an enzyme located in the plasma membrane of most eukaryotic cells, responsible for maintaining ion concentration gradients against their concentration scale using ATP hydrolysis as a source of energy. The enzyme is involved in many cellular activities, including maintaining cell volume, transporting nutrition, electrical potential, neurotransmission, and any dysfunction or modification of enzyme activity is directly linked to many diseases, such as epilepsy, cardiovascular disease and hypertension, diabetes and other metabolic disorders, digoxin toxicity, fetal abnormalities, neurological disorders, and pulmonary conditions. In this book, the authors present current research on regulation strategies, Na⁺/K⁺-ATPase as a biomarker in diseased states, and the use of Na⁺/K⁺-ATPase in the physiological and ecological adaptations of insects. Other topics discussed in this compilation include the effects of hormonal and non-hormonal stimulation on Na+/K+-ATPase activity, the physiology and pathophysiology of Na+/K+-ATPase, Na⁺/K⁺-ATPase as a biomarker for energy metabolism and oxidative stress in diseased states, the neurotensin inhibitory effects of [3H]-Ouabain binding to striatal membranes and inversion by administration of clozapine, and Na+/K+-ATPase's important functional roles in human body.




Regulation of Membrane Na+-K+ ATPase


Book Description

Na+-K+ ATPase or Na-pump ATPase, a member of “P”-type ATPase superfamily, is characterized by association of multiple isoforms mainly of it’s α- and β- subunits. At present four different α- (α-1,α-2,α-3 and α-4) and three β- (β-1, β-2, and β-3) isoforms have been identified in mammalian cells and their differential expressions are tissue specific. Regulation of Na+-K+ ATPase activity is an important but a complex process, which involves short-term and long-term mechanisms. Short-term regulation of Na+-K+ ATPase is either mediated by changes in intracellular Na+ concentrations that directly affect the Na+-pump activity or by phosphorylation/dephosphorylation-mediated by some stimulants leading to changes in its expression and transport properties. On the other hand, long-term regulation of Na+-K+ ATPase is mediated by hormones, such as mineralocorticoids and thyroid hormones, which cause changes in the transcription of genes of α- and β- subunits leading to an increased expression in the level of Na+-pump. Several studies have revealed a relatively new type of regulation that involves the association of small, single span membrane proteins with this enzyme. These proteins belong to the FXYD family, the members of which share a common signature sequence encompassing the transmembra ne domain adjacent to the isoform(s) of α-β subunits of Na+-K+ ATPase. Considering the extraordinary importance of Na+-K+ ATPase in cellular function, several internationally established investigators have contributed their articles in the monograph entitled “Regulation of Membrane Na+-K+ ATPase” for inspiring young scientists and graduate students to enrich their knowledge on the enzyme, and we are sure that this book will soon be considered as a comprehensive scientific literature in the area of Na+-K+ ATPase regulation in health and disease.




The Na, K-ATPase


Book Description

This text addresses the question, How does the sodium pump pump'. A variety of primary structure information is available, and progress has been made in the functional characterization of the Na, K-pump, making the answer to this question possible, within reach of currently used techniques




Cardiac Glycosides 1785–1985


Book Description

The bicentenary of William Withering's now famous medical report entitled "An Account of the Foxglove and Some of its Medical Uses" has given us the occasion to analyze the state of the art. Cardiac glycosides in 1985 are considered tobe the basis for medical treatment of myocardial failure, together with diuretics and vasodilators in the more severe cases. Nevertheless, the controversy as to their exact place in the treatment of heart failure with sinus rhythm has never ceased. Although cardiac glycosides are of unquestionable value in tachycardia caused by atrial fibrillation or atrial flutter, the chronic use of these drugs in sinus rhythm is not generally accepted. The development of tolerance has been reported. It is of interest that Withering hirnself wrote: "-let it (foxglove) be continued until it either acts on the kidneys, the stomach, the pulse, or the bowels; Iet it be stopped upon the first appearance of any of these effects, and I will maintain that the patient will not suffer from its exhibition, nor the practitioner be disappointed in any reasonable expectation. " In West Germany alone, more than three million patients (about 5% of the total population) are constantly taking cardiac glycosides. These drugs are the most prescribed medicaments in many countries. Thus, we considered it worthwhile and necessary to review in a critical way today's knowledge about the foxglove; to report new findings and to evaluate old Statements.




Na, K-ATPase and Related Cation Pumps


Book Description

This text focuses on research on the structure, molecular mechanisms, physiological regulation, and involvement in disease of Na, K-ATPase and other members of the family of cation pumps. Prominent members of this family include gastric H, K-ATPase, Ca-ATPase of sarcoplasmic and endoplasmic reticulum, plasma membrane Ca-ATPase, and plasma membrane of H-ATPase of fungi and higher plants, as well as heavy metal pumps. The volume includes details of the first high-resolution structure ever obtained of a P-type pump, the sarcoplasmic reticulum Ca-ATPase; this structure has great predictive power relative to all P-type pumps. There are 50 papers and 97 poster papers altogethe







Ion-motive ATPases


Book Description

The large body of recent knowledge that has allowed the recent discovery of new ATPases and the partial clarification of structural and functional aspects of the already known ATPases are the subjects of this volume. A dozen ION-MOTIVE ATPases are discussed in terms of structure, site modification, catalysis, expression, hormonal and metabolic regulation and pharmacologic intervention.




The Na, K-ATPase


Book Description




The Sodium Pump


Book Description

The sodium of animal cell membranes converts the chemical energy obtained from the hydrolysis of adenosine 5' -triphosphate into a movement of the cations Na + and K + against an electrochemical gradient. The gradient is used subse quently as an energy source to drive the uptake of metabolic substrates in polar epithelial cells and to use it for purposes of communications in excitable cells. The biological importance of the sodium pump is evident from the fact that be tween 20-70% of the cell's metabolic energy is consumed for the pumping pro cess. Moreover, the sodium pump is an important biological system involved in regulatory processes like the maintenance of the cells' and organism's water me tabolism. It is therefore understandable that special cellular demands are han dled better by special isoforms of the sodium pump, that the expression of the sodium pump and their isoforms is regulated by hormones as is the activity of the sodium pump via hormone-regulated protein kinases. Additionally, the sodium pump itself seems to be a receptor for a putative new group of hormones, the endogenous digitalis-like substances, which still have to be defined in most cases in their structure. This group of substances has its chemically well known coun terpart in steroids from plant and toad origin which are generally known as "car diac glycosides". They are in medical use since at least 200 years in medicine in the treatment of heart diseases.




Electrogenic Ion Pumps


Book Description

Electrogenic ion pumps convert chemical, reduction-oxidation, or light energy- into ion concentration differences across all living cells. They are the engines that run cells. In this text, Dr Lunger develops the principles of physical chemistry required to understand the functions of these macromolecules.