The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Lawrence G. Palmer - One of the best experts on this subject based on the ideXlab platform.
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Potassium Restriction downregulates romk expression in rat kidney
American Journal of Physiology-renal Physiology, 2000Co-Authors: Patricia A Mennitt, Gustavo Frindt, Randi B Silver, Lawrence G. PalmerAbstract:The ROMK family of proteins has biophysical properties and distribution within the kidney similar to those of secretory Potassium channels of the distal nephron. To study the regulation of ROMK during variations in dietary Potassium, we measured the abundance of ROMK protein in rat kidney by immunoblotting. Neither 2 nor 5 days of a high-Potassium diet had an effect on protein abundance in the cortex or medulla. Potassium deprivation (2 or 5 days) decreased ROMK protein content in both cortical and medullary fractions, to 51 and 40% of controls, respectively. To see whether the Na-K-2Cl cotransporter is similarly affected by Potassium Restriction, we analyzed immunoblots by using an antibody for the rat type 1 bumetanide-sensitive cotransporter (BSC-1). Like ROMK, BSC-1 protein content was found to decrease significantly in the renal medulla of Potassium-deprived rats. In the thick ascending limb of Henle's loop, a decrease in ROMK and BSC-1 could result in decreased reabsorption of NaCl, a finding associated with hypokalemia.
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Potassium Restriction downregulates romk expression in rat kidney
American Journal of Physiology-renal Physiology, 2000Co-Authors: Patricia A Mennitt, Gustavo Frindt, Randi B Silver, Lawrence G. PalmerAbstract:The ROMK family of proteins has biophysical properties and distribution within the kidney similar to those of secretory Potassium channels of the distal nephron. To study the regulation of ROMK dur...
Patricia A Mennitt - One of the best experts on this subject based on the ideXlab platform.
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Potassium Restriction downregulates romk expression in rat kidney
American Journal of Physiology-renal Physiology, 2000Co-Authors: Patricia A Mennitt, Gustavo Frindt, Randi B Silver, Lawrence G. PalmerAbstract:The ROMK family of proteins has biophysical properties and distribution within the kidney similar to those of secretory Potassium channels of the distal nephron. To study the regulation of ROMK during variations in dietary Potassium, we measured the abundance of ROMK protein in rat kidney by immunoblotting. Neither 2 nor 5 days of a high-Potassium diet had an effect on protein abundance in the cortex or medulla. Potassium deprivation (2 or 5 days) decreased ROMK protein content in both cortical and medullary fractions, to 51 and 40% of controls, respectively. To see whether the Na-K-2Cl cotransporter is similarly affected by Potassium Restriction, we analyzed immunoblots by using an antibody for the rat type 1 bumetanide-sensitive cotransporter (BSC-1). Like ROMK, BSC-1 protein content was found to decrease significantly in the renal medulla of Potassium-deprived rats. In the thick ascending limb of Henle's loop, a decrease in ROMK and BSC-1 could result in decreased reabsorption of NaCl, a finding associated with hypokalemia.
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Potassium Restriction downregulates romk expression in rat kidney
American Journal of Physiology-renal Physiology, 2000Co-Authors: Patricia A Mennitt, Gustavo Frindt, Randi B Silver, Lawrence G. PalmerAbstract:The ROMK family of proteins has biophysical properties and distribution within the kidney similar to those of secretory Potassium channels of the distal nephron. To study the regulation of ROMK dur...
Wenhui Wang - One of the best experts on this subject based on the ideXlab platform.
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Deletion of Kir5.1 Impairs Renal Ability to Excrete Potassium During Increased Dietary Potassium Intake
Journal of The American Society of Nephrology, 2019Co-Authors: Peng Wu, Xiao-tong Su, Dan-dan Zhang, Wenhui WangAbstract:Background The basolateral Potassium channel in the distal convoluted tubule (DCT), comprising the inwardly rectifying Potassium channel Kir4.1/Kir5.1 heterotetramer, plays a key role in mediating the effect of dietary Potassium intake on the thiazide-sensitive NaCl cotransporter (NCC). The role of Kir5.1 (encoded by Kcnj16) in mediating effects of dietary Potassium intake on the NCC and renal Potassium excretion is unknown. Methods We used electrophysiology, renal clearance, and immunoblotting to study Kir4.1 in the DCT and NCC in Kir5.1 knockout (Kcnj16-/- ) and wild-type (Kcnj16+/+ ) mice fed with normal, high, or low Potassium diets. Results We detected a 40-pS and 20-pS Potassium channel in the basolateral membrane of the DCT in wild-type and knockout mice, respectively. Compared with wild-type, Kcnj16-/- mice fed a normal Potassium diet had higher basolateral Potassium conductance, a more negative DCT membrane potential, higher expression of phosphorylated NCC (pNCC) and total NCC (tNCC), and augmented thiazide-induced natriuresis. Neither high- nor low-Potassium diets affected the basolateral DCT's Potassium conductance and membrane potential in Kcnj16-/- mice. Although high Potassium reduced and low Potassium increased the expression of pNCC and tNCC in wild-type mice, these effects were absent in Kcnj16-/- mice. High Potassium intake inhibited and low intake augmented thiazide-induced natriuresis in wild-type but not in Kcnj16-/- mice. Compared with wild-type, Kcnj16-/- mice with normal Potassium intake had slightly lower plasma Potassium but were more hyperkalemic with prolonged high Potassium intake and more hypokalemic during Potassium Restriction. Conclusions Kir5.1 is essential for dietary Potassium's effect on NCC and for maintaining Potassium homeostasis.
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Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 Potassium channel.
Kidney International, 2018Co-Authors: Ming Xiao Wang, Wenhui Wang, Xiao-tong Su, James A. Mccormick, Catherina A. Cuevas, Peng Wu, Chao Ling Yang, David H. EllisonAbstract:Kir4.1 in the distal convoluted tubule plays a key role in sensing plasma Potassium and in modulating the thiazide-sensitive sodium-chloride cotransporter (NCC). Here we tested whether dietary Potassium intake modulates Kir4.1 and whether this is essential for mediating the effect of Potassium diet on NCC. High Potassium intake inhibited the basolateral 40 pS Potassium channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule, decreased basolateral Potassium conductance, and depolarized the distal convoluted tubule membrane in Kcnj10flox/flox mice, herein referred to as control mice. In contrast, low Potassium intake activated Kir4.1, increased Potassium currents, and hyperpolarized the distal convoluted tubule membrane. These effects of dietary Potassium intake on the basolateral Potassium conductance and membrane potential in the distal convoluted tubule were completely absent in inducible kidney-specific Kir4.1 knockout mice. Furthermore, high Potassium intake decreased, whereas low Potassium intake increased the abundance of NCC expression only in the control but not in kidney-specific Kir4.1 knockout mice. Renal clearance studies demonstrated that low Potassium augmented, while high Potassium diminished, hydrochlorothiazide-induced natriuresis in control mice. Disruption of Kir4.1 significantly increased basal urinary sodium excretion but it abolished the natriuretic effect of hydrochlorothiazide. Finally, hypokalemia and metabolic alkalosis in kidney-specific Kir4.1 knockout mice were exacerbated by Potassium Restriction and only partially corrected by a high-Potassium diet. Thus, Kir4.1 plays an essential role in mediating the effect of dietary Potassium intake on NCC activity and Potassium homeostasis.
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expression of tetraspan protein cd63 activates protein tyrosine kinase ptk and enhances the ptk induced inhibition of romk channels
Journal of Biological Chemistry, 2008Co-Authors: Erik-jan Kamsteeg, Hyacinth Sterling, Amy S Duffield, Joanna Spencer, Marcel Roos, Michael S. Caplan, Yan Zhang, Wenhui WangAbstract:Abstract In the present study, we tested the role of CD63 in regulating ROMK1 channels by protein-tyrosine kinase (PTK). Immunocytochemical staining shows that CD63 and receptor-linked tyrosine phosphatase α (RPTPα) are expressed in the cortical collecting duct and outer medulla collecting duct. Immunoprecipitation of tissue lysates from renal cortex and outer medulla or 293T cells transfected with CD63 reveals that CD63 was associated with RPTPα both in situ and in transfected cells. Expression of CD63 in 293T cells stimulated the phosphorylation of tyrosine residue 416 of c-Src but decreased the phosphorylation of tyrosine residue 527, indicating that expression of CD63 stimulates the activity of c-Src. Furthermore, c-Src was coimmunoprecipitated with RPTPα and CD63 both in 293T cells transfected with CD63 and in lysates prepared from native rat kidney. Potassium Restriction had no effect on the expression of RPTPα, but it increased the association between c-Src and RPTPα in the renal cortex and outer medulla. We also used two-electrode voltage clamp to study the effect of CD63 on ROMK channels in Xenopus oocytes. Expression of CD63 had no significant effect on Potassium currents in oocytes injected with ROMK1; however, it significantly enhanced the c-Src-induced inhibition of ROMK channels in oocytes injected with ROMK1+c-Src. The effect of CD63 on the c-Src-induced inhibition was not due to a decreased expression of ROMK1 channels, because blocking PTK with herbimycin A abolished the inhibitory effect of c-Src on ROMK channels in oocytes injected with ROMK1+c-Src+CD63. Furthermore, coexpression of CD63 enhanced tyrosine phosphorylation of ROMK1. We conclude that CD63 plays a role in the regulation of ROMK channels through its association with RPTPα, which in turn interacts with and activates Src family PTK, thus reducing ROMK activity.
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angiotensin ii inhibits the romk like small conductance k channel in renal cortical collecting duct during dietary Potassium Restriction
Journal of Biological Chemistry, 2007Co-Authors: Beth Zavilowitz, Lisa M Satlin, Wenhui WangAbstract:Abstract Base-line urinary Potassium secretion in the distal nephron is mediated by small conductance rat outer medullary K (ROMK)-like channels. We used the patch clamp technique applied to split-open cortical collecting ducts (CCDs) isolated from rats fed a normal Potassium (NK) or low Potassium (LK) diet to test the hypothesis that AngII directly inhibits ROMK channel activity. We found that AngII inhibited ROMK channel activity in LK but not NK rats in a dose-dependent manner. The AngII-induced reduction in channel activity was mediated by AT1 receptor (AT1R) binding, because pretreatment of CCDs with losartan but not PD123319 AT1 and AT2 receptor antagonists, respectively, blocked the response. Pretreatment of CCDs with U73122 and calphostin C, inhibitors of phospholipase C (PLC) and protein kinase C (PKC), respectively, abolished the AngII-induced decrease in ROMK channel activity, confirming a role of the PLC-PKC pathway in this response. Studies by others suggest that AngII stimulates an Src family protein-tyrosine kinase (PTK) via PKC-NADPH oxidase. PTK has been shown to regulate the ROMK channel. Inhibition of NADPH oxidase with diphenyliodonium abolished the inhibitory effect of AngII or the PKC activator phorbol 12-myristate 13-acetate on ROMK channels. Suppression of PTK by herbimycin A significantly attenuated the inhibitory effect of AngII on ROMK channel activity. We conclude that AngII inhibits ROMK channel activity through PKC-, NADPH oxidase-, and PTK-dependent pathways under conditions of dietary Potassium Restriction.
Gustavo Frindt - One of the best experts on this subject based on the ideXlab platform.
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Potassium Restriction downregulates romk expression in rat kidney
American Journal of Physiology-renal Physiology, 2000Co-Authors: Patricia A Mennitt, Gustavo Frindt, Randi B Silver, Lawrence G. PalmerAbstract:The ROMK family of proteins has biophysical properties and distribution within the kidney similar to those of secretory Potassium channels of the distal nephron. To study the regulation of ROMK during variations in dietary Potassium, we measured the abundance of ROMK protein in rat kidney by immunoblotting. Neither 2 nor 5 days of a high-Potassium diet had an effect on protein abundance in the cortex or medulla. Potassium deprivation (2 or 5 days) decreased ROMK protein content in both cortical and medullary fractions, to 51 and 40% of controls, respectively. To see whether the Na-K-2Cl cotransporter is similarly affected by Potassium Restriction, we analyzed immunoblots by using an antibody for the rat type 1 bumetanide-sensitive cotransporter (BSC-1). Like ROMK, BSC-1 protein content was found to decrease significantly in the renal medulla of Potassium-deprived rats. In the thick ascending limb of Henle's loop, a decrease in ROMK and BSC-1 could result in decreased reabsorption of NaCl, a finding associated with hypokalemia.
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Potassium Restriction downregulates romk expression in rat kidney
American Journal of Physiology-renal Physiology, 2000Co-Authors: Patricia A Mennitt, Gustavo Frindt, Randi B Silver, Lawrence G. PalmerAbstract:The ROMK family of proteins has biophysical properties and distribution within the kidney similar to those of secretory Potassium channels of the distal nephron. To study the regulation of ROMK dur...
Randi B Silver - One of the best experts on this subject based on the ideXlab platform.
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Potassium Restriction downregulates romk expression in rat kidney
American Journal of Physiology-renal Physiology, 2000Co-Authors: Patricia A Mennitt, Gustavo Frindt, Randi B Silver, Lawrence G. PalmerAbstract:The ROMK family of proteins has biophysical properties and distribution within the kidney similar to those of secretory Potassium channels of the distal nephron. To study the regulation of ROMK during variations in dietary Potassium, we measured the abundance of ROMK protein in rat kidney by immunoblotting. Neither 2 nor 5 days of a high-Potassium diet had an effect on protein abundance in the cortex or medulla. Potassium deprivation (2 or 5 days) decreased ROMK protein content in both cortical and medullary fractions, to 51 and 40% of controls, respectively. To see whether the Na-K-2Cl cotransporter is similarly affected by Potassium Restriction, we analyzed immunoblots by using an antibody for the rat type 1 bumetanide-sensitive cotransporter (BSC-1). Like ROMK, BSC-1 protein content was found to decrease significantly in the renal medulla of Potassium-deprived rats. In the thick ascending limb of Henle's loop, a decrease in ROMK and BSC-1 could result in decreased reabsorption of NaCl, a finding associated with hypokalemia.
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Potassium Restriction downregulates romk expression in rat kidney
American Journal of Physiology-renal Physiology, 2000Co-Authors: Patricia A Mennitt, Gustavo Frindt, Randi B Silver, Lawrence G. PalmerAbstract:The ROMK family of proteins has biophysical properties and distribution within the kidney similar to those of secretory Potassium channels of the distal nephron. To study the regulation of ROMK dur...