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Renal aquaporins: physiology and pathophysiology
S 11()
Abstracts / Comparative Biochemistry and Physiology, P.rt A 126 (2000) S I - S I 6 3
RENAL AQUAPORINS: P H Y S I O L O G Y AND P A T H O P H Y S I O L O G Y N i e l s e n S., Frokia~r J., M a r p l e s D., K w o n T - H . , P r o m e n e u r D., C h r i s t e n s e n B., N e j s u m L., Elkja~r M . L . and K n e p p e r M. U n i v . o f A a r h u s , A a r h u s , D e n m a r k , Dept. Biol. C h e m . , J o h n s H o p k i n s U n i v . M e d . S c h o o l , B a l t i m o r e , M D , U S A and L K E M , N H L B I , N I H , B e t h e s d a , M D , U S A . The discovery of aquaporin-I (AQP1), by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. AQPI is abundant in the proximal nephron and represents the major constitutive water channel of the nephron. AQP2 is the predominant vasopressin regulated water channel of the kidney collecting duct. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells representing exit pathways. AQP6, AQP7, AQP8 and AQP9 are also present in kidney but remain uncharacterized.Body water balance is tightly regulated by vasopressin and multiple studies now have underscored the essential role of AQP2 for vasopressin regulation of body water balance. Vasopressin regulates acutely the water permeability of the kidney collecting duct by reversible translocation of AQP2 from intracellular vesicles to the apical plasma membrane. Phosphorylation of AQP2 by PKA is criticially involved in this. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus and reduced expression is seen in several common forms of acquired nephrogenic diabetes insipidus including lithium treatment, hypokalemia, hypercalcemia and postobstructive polyuria. In contrast, in conditions with water retention such as severe congestive heart failure and pregnancy both AQP2 expression levels and apical plasma membrane targetting is increased suggesting a role for AQP2 in the development of water retention. Experimentally induced chronic renal failure, ischemia-induced acute renal failure and nephrotic syndrome in rats are also associated with dysregulation of AQP2. Continued analysis of the aquaporins provides detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
O X Y G E N - D E P E N D E N T ION T R A N S P O R T N i k i n m a a M. and B o g d a n o v a A.Y. Department of Biology, University of Turku, FIN-20014 Turku, Finland Studies mainly on excitable cells and on erythrocytes from several species have shown that transport of various ions across cell membrane is affected by oxygen tension. In several excitable cell types hypoxia causes a pronounced, immediate inhibition of potassium channels. Also the isotonic potassium channel and the osmotically activated chloride channel of lamprey erythrocytes, the potassium-chloride cotransporter of teleost erythrocytes and sodium-potassium-chloride cotransporter of alveolar epithelial cells, calcium channels of smooth muscle cells and sodium channels of pneumocytes are inhibited by hypoxic conditions. On the other hand, the sodium/proton exchanger of fish erythrocytes, the ATP-sensitive potassium channels of smooth muscle, and one type of sodium channels in rat cardiac myocytes5° are activated by low oxygen levels. The effects of oxygen on the transporters may be mediated via reactive oxygen species (ROS) or (more generally) the redox state of the cell The simplest explanation for the modification of transporter activity by the redox state of the cell is that sulphydryl groups are critical for the function of the transporter. Indeed, sulphydryl modification markedly influences the activity of the potassium chloride cotransporter the activity of which is often strongly influenced by oxygen. Using primary cultures of rainbow trout hepatocytes, and the fluorescent dye H2-DCFDA, we have shown that hydrogen peroxide production increases markedly when oxygen tension increases at the physiological oxygen range from 1 to 20 % 02 These data, and the observation that potassium-chloride cotransport of teleost erythrocytes is markedly inhibited by hydroxyl ion scavengers, suggest that, indeed, the effects of oxygen on fish ion transporters may be mediated via ROS.
Abstracts / Comparative Biochemistry and Physiology, P.rt A 126 (2000) S I - S I 6 3
RENAL AQUAPORINS: P H Y S I O L O G Y AND P A T H O P H Y S I O L O G Y N i e l s e n S., Frokia~r J., M a r p l e s D., K w o n T - H . , P r o m e n e u r D., C h r i s t e n s e n B., N e j s u m L., Elkja~r M . L . and K n e p p e r M. U n i v . o f A a r h u s , A a r h u s , D e n m a r k , Dept. Biol. C h e m . , J o h n s H o p k i n s U n i v . M e d . S c h o o l , B a l t i m o r e , M D , U S A and L K E M , N H L B I , N I H , B e t h e s d a , M D , U S A . The discovery of aquaporin-I (AQP1), by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. AQPI is abundant in the proximal nephron and represents the major constitutive water channel of the nephron. AQP2 is the predominant vasopressin regulated water channel of the kidney collecting duct. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells representing exit pathways. AQP6, AQP7, AQP8 and AQP9 are also present in kidney but remain uncharacterized.Body water balance is tightly regulated by vasopressin and multiple studies now have underscored the essential role of AQP2 for vasopressin regulation of body water balance. Vasopressin regulates acutely the water permeability of the kidney collecting duct by reversible translocation of AQP2 from intracellular vesicles to the apical plasma membrane. Phosphorylation of AQP2 by PKA is criticially involved in this. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus and reduced expression is seen in several common forms of acquired nephrogenic diabetes insipidus including lithium treatment, hypokalemia, hypercalcemia and postobstructive polyuria. In contrast, in conditions with water retention such as severe congestive heart failure and pregnancy both AQP2 expression levels and apical plasma membrane targetting is increased suggesting a role for AQP2 in the development of water retention. Experimentally induced chronic renal failure, ischemia-induced acute renal failure and nephrotic syndrome in rats are also associated with dysregulation of AQP2. Continued analysis of the aquaporins provides detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
O X Y G E N - D E P E N D E N T ION T R A N S P O R T N i k i n m a a M. and B o g d a n o v a A.Y. Department of Biology, University of Turku, FIN-20014 Turku, Finland Studies mainly on excitable cells and on erythrocytes from several species have shown that transport of various ions across cell membrane is affected by oxygen tension. In several excitable cell types hypoxia causes a pronounced, immediate inhibition of potassium channels. Also the isotonic potassium channel and the osmotically activated chloride channel of lamprey erythrocytes, the potassium-chloride cotransporter of teleost erythrocytes and sodium-potassium-chloride cotransporter of alveolar epithelial cells, calcium channels of smooth muscle cells and sodium channels of pneumocytes are inhibited by hypoxic conditions. On the other hand, the sodium/proton exchanger of fish erythrocytes, the ATP-sensitive potassium channels of smooth muscle, and one type of sodium channels in rat cardiac myocytes5° are activated by low oxygen levels. The effects of oxygen on the transporters may be mediated via reactive oxygen species (ROS) or (more generally) the redox state of the cell The simplest explanation for the modification of transporter activity by the redox state of the cell is that sulphydryl groups are critical for the function of the transporter. Indeed, sulphydryl modification markedly influences the activity of the potassium chloride cotransporter the activity of which is often strongly influenced by oxygen. Using primary cultures of rainbow trout hepatocytes, and the fluorescent dye H2-DCFDA, we have shown that hydrogen peroxide production increases markedly when oxygen tension increases at the physiological oxygen range from 1 to 20 % 02 These data, and the observation that potassium-chloride cotransport of teleost erythrocytes is markedly inhibited by hydroxyl ion scavengers, suggest that, indeed, the effects of oxygen on fish ion transporters may be mediated via ROS.