scholarly journals The Pharmacological Inhibition of CaMKII Regulates Sodium Chloride Cotransporter Activity in mDCT15 Cells

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1335
Author(s):  
Mohammed F. Gholam ◽  
Benjamin Ko ◽  
Zinah M. Ghazi ◽  
Robert S. Hoover ◽  
Abdel A. Alli
Keyword(s):  
Sodium Chloride ◽  
Actin Cytoskeleton ◽  
Active Form ◽  
Direct Interaction ◽  
Feedback Mechanism ◽  
Distal Convoluted Tubule ◽  
Filamin A ◽  
Pharmacological Inhibition ◽  
Luminal Membrane ◽  
Sodium Chloride Cotransporter

The thiazide-sensitive sodium chloride cotransporter (NCC) in the distal convoluted tubule is responsible for reabsorbing up to one-tenth of the total filtered load of sodium in the kidney. The actin cytoskeleton is thought to regulate various transport proteins in the kidney but the regulation of the NCC by the actin cytoskeleton is largely unknown. Here, we identify a direct interaction between the NCC and the cytoskeletal protein filamin A in mouse distal convoluted tubule (mDCT15) cells and in the native kidney. We show that the disruption of the actin cytoskeleton by two different mechanisms downregulates NCC activity. As filamin A is a substrate of the Ca2+/calmodulin-dependent protein kinase II (CaMKII), we investigate the physiological significance of CaMKII inhibition on NCC luminal membrane protein expression and NCC activity in mDCT15 cells. The pharmacological inhibition of CaMKII with the compound KN93 increases the active form of the NCC (phospho-NCC) at the luminal membrane and also increases NCC activity in mDCT15 cells. These data suggest that the interaction between the NCC and filamin A is dependent on CaMKII activity, which may serve as a feedback mechanism to maintain basal levels of NCC activity in the distal nephron.

scholarly journals Activation of the Thiazide-Sensitive Sodium-Chloride Cotransporter by Beta3-Adrenoreceptor in the Distal Convoluted Tubule

2021 ◽  
Vol 12 ◽  
Author(s):  
Serena Milano ◽  
Monica Carmosino ◽  
Andrea Gerbino ◽  
Ilenia Saponara ◽  
Dominga Lapi ◽  
...  
Keyword(s):  
Sodium Chloride ◽  
Adrenergic Receptor ◽  
Wild Type Mouse ◽  
Mouse Kidney ◽  
Distal Convoluted Tubule ◽  
Wild Type ◽  
Sodium Chloride Cotransporter ◽  
Antidiuretic Effect ◽  
Significant Attenuation

We previously showed that the beta-3 adrenergic receptor (BAR3) is expressed in most segments of the nephron where its agonism promotes a potent antidiuretic effect. We localized BAR3 in distal convoluted tubule (DCT) cells expressing the thiazide-sensitive sodium-chloride cotransporter (NCC). Aim of this study is to investigate the possible functional role of BAR3 on NCC modulation in DCT cells. Here, we found that, in mice, the knockout of BAR3 was paralleled by a significant attenuation of NCC phosphorylation, paralleled by reduced expression and activation of STE-20/SPS1-related proline-alanine-rich kinase (SPAK) and WNKs the main kinases involved in NCC activation. Conversely, in BAR1/2 knockout mice, we found reduced NCC abundance with no changes in the phosphorylation state of NCC. Moreover, selective BAR3 agonism promotes both SPAK and NCC activation in wild-type mouse kidney slices. In conclusion, our findings suggest a novel role for BAR3 in the regulation of NCC in DCT.

scholarly journals Uromodulin is expressed in the distal convoluted tubule, where it is critical for regulation of the sodium chloride cotransporter NCC

2018 ◽  
Vol 94 (4) ◽  
pp. 701-715 ◽  
Author(s):  
Natsuko Tokonami ◽  
Tomoaki Takata ◽  
Jan Beyeler ◽  
Iris Ehrbar ◽  
Ayumi Yoshifuji ◽  
...  
Keyword(s):  
Sodium Chloride ◽  
Distal Convoluted Tubule ◽  
Sodium Chloride Cotransporter

scholarly journals Vasopressin induces phosphorylation of the thiazide-sensitive sodium chloride cotransporter in the distal convoluted tubule

2010 ◽  
Vol 78 (2) ◽  
pp. 160-169 ◽  
Author(s):  
Nis B. Pedersen ◽  
Marlene V. Hofmeister ◽  
Lena L. Rosenbaek ◽  
Jakob Nielsen ◽  
Robert A. Fenton
Keyword(s):  
Sodium Chloride ◽  
Distal Convoluted Tubule ◽  
Sodium Chloride Cotransporter

Luminal influences on potassium secretion: chloride, sodium, and thiazide diuretics

1992 ◽  
Vol 262 (6) ◽  
pp. F1076-F1082 ◽  
Author(s):  
H. Velazquez ◽  
D. H. Ellison ◽  
F. S. Wright
Keyword(s):  
Distal Tubule ◽  
Distal Convoluted Tubule ◽  
Thiazide Diuretics ◽  
Maximal Level ◽  
Luminal Membrane ◽  
K Secretion ◽  
Potassium Secretion

In the presence of Cl-, K+ secretion by the distal tubule saturates with increasing luminal Na+ concentration. Apparent maximal K+ secretion is attained with luminal Na+ concentrations of 40 mM. The results of the present study show that lowering the Cl- concentration of luminal fluid can increase the level of Na(+)-stimulated K+ secretion beyond the maximal level attained in the presence of Cl-. The effect of lowering luminal Cl- concentration to less than 10 mM on K+ secretion is greater with higher Na+ concentration. Under these conditions, chlorothiazide decreases K+ secretion. When chlorothiazide is present, changing the Na+ concentration does not affect K+ secretion. Because in rats a thiazide effect is attributed primarily to the distal convoluted tubule (DCT), we postulate that it is primarily DCT cells that increase K+ secretion when Na+ concentration is raised in the presence of low luminal Cl- concentration. We propose that the rat DCT cells have both an absorptive Na(+)-Cl- cotransport mechanism and a secretory K(+)-Cl- cotransport mechanism in the luminal membrane that can mediate the apparent exchange of Na+ for K+.

scholarly journals Publisher Correction: IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A

2018 ◽  
Vol 20 (10) ◽  
pp. 1228-1228
Author(s):  
Hery Urra ◽  
Daniel R. Henriquez ◽  
José Cánovas ◽  
David Villarroel-Campos ◽  
Amado Carreras-Sureda ◽  
...  
Keyword(s):  
Cell Migration ◽  
Direct Interaction ◽  
Filamin A
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