scholarly journals Exploration of the Basolateral Chloride Channels in the Renal Tubule using

2005 ◽  
Vol 99 (2) ◽  
pp. p64-p68 ◽  
Author(s):  
Jacques Teulon ◽  
Stéphane Lourdel ◽  
Antoine Nissant ◽  
Marc Paulais ◽  
Romain Guinamard ◽  
...  

1997 ◽  
Vol 272 (5) ◽  
pp. F678-F688 ◽  
Author(s):  
A. Vandewalle ◽  
F. Cluzeaud ◽  
M. Bens ◽  
S. Kieferle ◽  
K. Steinmeyer ◽  
...  

We investigate the intrarenal expression of two recently cloned chloride channels, rClC-K1 and rClC-K2, by reverse transcriptase-polymerase chain reaction on single microdissected tubules from the rat kidney and by immunohistochemistry using a polyclonal antibody that recognizes both highly homologous channels. Both rClC-K1 and rClC-K2 mRNAs were detected in outer medullary late proximal tubules (S3), papillary ascending thin limbs (ATL), and outer medullary (MTAL) and cortical (CTAL) thick ascending limbs, distal tubules (DCT), and cortical, outer medullary, and inner medullary collecting ducts. Indirect immunofluorescence studies demonstrated that the rClC-K proteins were restricted to the basolateral membranes from ATL, DCT, and collecting ducts cells, whereas CTAL and MTAL exhibited a more diffuse basal staining. When rats were dehydrated, a condition which increased the expression of rClC-K1 in cortex and medulla, a weak cytoplasmic staining was found in late proximal tubule cells. Thus these results demonstrate that rat kidney ClC-K channels are predominantly located in the basolateral membranes from cells of the late segments of the renal tubule where most of chloride reabsorption takes place.



Author(s):  
Dun Niu ◽  
Lanfang Li ◽  
Zhizhong Xie

Chloride channel 3 (ClC-3), a Cl−/H+ antiporter, has been well established as a member of volume-regulated chloride channels (VRCCs). ClC-3 may be a crucial mediator for activating inflammation-associated signaling pathways by regulating protein phosphorylation. A growing number of studies have indicated that ClC-3 overexpression plays a crucial role in mediating increased plasma low-density lipoprotein levels, vascular endothelium dysfunction, pro-inflammatory activation of macrophages, hyper-proliferation and hyper-migration of vascular smooth muscle cells (VSMCs), as well as oxidative stress and foam cell formation, which are the main factors responsible for atherosclerotic plaque formation in the arterial wall. In the present review, we summarize the molecular structures and classical functions of ClC-3. We further discuss its emerging role in the atherosclerotic process. In conclusion, we explore the potential role of ClC-3 as a therapeutic target for atherosclerosis.



Author(s):  
Yoshihisa Ozoe

Abstract In the late 1970s, we discovered that toxic bicyclic phosphates inhibit the generation of miniature inhibitory junction potentials, implying their antagonism of γ-aminobutyric acid (GABA) receptors (GABARs; GABA-gated chloride channels). This unique mode of action provided a strong incentive for our research on GABARs in later years. Furthermore, minor structural changes conferred insect GABAR selectivity to this class of compounds, convincing us of the possibility of GABARs as targets for insecticides. Forty years later, third-generation insecticides acting as allosteric modulator antagonists at a distinctive site of action in insect GABARs were developed. G protein-coupled receptors (GPCRs) are also promising targets for pest control. We characterized phenolamine receptors functionally and pharmacologically. Of the tested receptors, β-adrenergic-like octopamine receptors were revealed to be the most sensitive to the acaricide/insecticide amitraz. Given the presence of multiple sites of action, ion channels and GPCRs remain potential targets for invertebrate pest control.



2010 ◽  
Vol 48 (1) ◽  
pp. 211-219 ◽  
Author(s):  
Dazhi Xiong ◽  
Nathanael S. Heyman ◽  
Judith Airey ◽  
Mi Zhang ◽  
Cherie A. Singer ◽  
...  


2021 ◽  
Vol 11 (2) ◽  
pp. 87-98
Author(s):  
Frederick Berro Rivera ◽  
Pia Alfonso ◽  
Jem Marie Golbin ◽  
Kevin Lo ◽  
Edgar Lerma ◽  
...  

Clinical guidelines include diuretics for the treatment of heart failure (HF), not to decrease mortality but to decrease symptoms and hospitalizations. More attention has been paid to the worse outcomes, including mortality, associated with continual diuretic therapy due to hypochloremia. Studies have revealed a pivotal role for serum chloride in the pathophysiology of HF and is now a target of treatment to decrease mortality. The prognostic value of serum chloride in HF has been the subject of much attention. Mechanistically, the macula densa, a region in the renal juxtaglomerular apparatus, relies on chloride levels to sense salt and volume status. The recent discovery of with-no-lysine (K) (WNK) protein kinase as an intracellular chloride sensor sheds light on the possible reason of diuretic resistance in HF. The action of chloride on WNKs results in the upregulation of the sodium-potassium-chloride cotransporter and sodium-chloride cotransporter receptors, which could lead to increased electrolyte and fluid reabsorption. Genetic studies have revealed that a variant of a voltage-sensitive chloride channel (CLCNKA) gene leads to almost a 50% decrease in current amplitude and function of the renal chloride channel. This variant increases the risk of HF. Several trials exploring the prognostic value of chloride in both acute and chronic HF have shown mostly positive results, some even suggesting a stronger role than sodium. However, so far, interventional trials exploring serum chloride as a therapeutic target have been largely inconclusive. This study is a review of the pathophysiologic effects of hypochloremia in HF, the genetics of chloride channels, and clinical trials that are underway to investigate novel approaches to HF management.



2005 ◽  
Vol 566 (1) ◽  
pp. 205-212 ◽  
Author(s):  
Min-Goo Lee ◽  
Donald W. MacGlashan ◽  
Bradley J. Undem
Keyword(s):  


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