Proinflammatory Cytokines and Potassium Channels in the Kidney

Proinflammatory cytokines affect several cell functions via receptor-mediated processes. In the kidney, functions of transporters and ion channels along the nephron are also affected by some cytokines. Among these, alteration of activity of potassium ion (K+) channels induces changes in transepithelial transport of solutes and water in the kidney, since K+channels in tubule cells are indispensable for formation of membrane potential which serves as a driving force for the transepithelial transport. Altered K+channel activity may be involved in renal cell dysfunction during inflammation. Although little information was available regarding the effects of proinflammatory cytokines on renal K+channels, reports have emerged during the last decade. In human proximal tubule cells, interferon-γshowed a time-dependent biphasic effect on a 40 pS K+channel, that is, delayed suppression and acute stimulation, and interleukin-1βacutely suppressed the channel activity. Transforming growth factor-β1 activated KCa3.1 K+channel in immortalized human proximal tubule cells, which would be involved in the pathogenesis of renal fibrosis. This review discusses the effects of proinflammatory cytokines on renal K+channels and the causal relationship between the cytokine-induced changes in K+channel activity and renal dysfunction.

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Involvement of Endogenous Nitric Oxide in the Regulation of K+ Channel Activity in Cultured Human Proximal Tubule Cells

The Journal of Physiological Sciences ◽

10.2170/physiolsci.rp003106 ◽

2006 ◽

Vol 56 (6) ◽

pp. 407-413 ◽

Cited By ~ 4

Author(s):

Kazuyoshi Nakamura ◽

Wataru Habano ◽

Toshiyuki Kojo ◽

You Komagiri ◽

Takahiro Kubota ◽

...

Keyword(s):

Nitric Oxide ◽

Proximal Tubule ◽

K Channel ◽

Channel Activity ◽

Proximal Tubule Cells ◽

Endogenous Nitric Oxide ◽

Tubule Cells ◽

Human Proximal Tubule

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The role of Krüppel-like factor 4 in transforming growth factor-β-induced inflammatory and fibrotic responses in human proximal tubule cells

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.12405 ◽

2015 ◽

Vol 42 (6) ◽

pp. 680-686 ◽

Cited By ~ 10

Author(s):

Ellein Mreich ◽

Xin-Ming Chen ◽

Amgad Zaky ◽

Carol A Pollock ◽

Sonia Saad

Keyword(s):

Growth Factor ◽

Proximal Tubule ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Proximal Tubule Cells ◽

Tubule Cells ◽

Human Proximal Tubule

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Protein kinase G activates inwardly rectifying K+ channel in cultured human proximal tubule cells

AJP Renal Physiology ◽

10.1152/ajprenal.00023.2002 ◽

2002 ◽

Vol 283 (4) ◽

pp. F784-F791 ◽

Cited By ~ 13

Author(s):

Kazuyoshi Nakamura ◽

Junko Hirano ◽

Shun-Ichi Itazawa ◽

Manabu Kubokawa

Keyword(s):

Proximal Tubule ◽

Specific Inhibitor ◽

K Channel ◽

Channel Activity ◽

Patch Clamp Technique ◽

Proximal Tubule Cells ◽

Bath Application ◽

Tubule Cells ◽

Inwardly Rectifying ◽

Human Proximal Tubule

An ATP-regulated inwardly rectifying K+ channel, whose activity is enhanced by PKA, is present in the plasma membrane of cultured human proximal tubule cells. In this study, we investigated the effects of PKG on this K+ channel, using the patch-clamp technique. In cell-attached patches, bath application of a membrane-permeant cGMP analog, 8-bromoguanosine 3′,5′-monophosphate (8-BrcGMP; 100 μM), stimulated channel activity, whereas application of a PKG-specific inhibitor, KT-5823 (1 μM), reduced the activity. Channel activation induced by 8-BrcGMP was observed even in the presence of a PKA-specific inhibitor, KT-5720 (500 nM), which was abolished by KT-5823. Direct effects of cGMP and PKG were examined with inside-out patches in the presence of 1 mM MgATP. Although cytoplasmic cGMP (100 μM) alone had little effect on channel activity, subsequent addition of PKG (500 U/ml) enhanced it. Furthermore, bath application of atrial natriuretic peptide (ANP; 20 nM) in cell-attached patches stimulated channel activity, which was blocked by KT-5823. In conclusion, cGMP/PKG-dependent processes participate in activating the ATP-regulated K+ channel and producing the stimulatory effect of ANP on channel activity.

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Nephrotoxicity Testing In Vitro: The Current Situation

Alternatives to Laboratory Animals ◽

10.1177/026119299702500506 ◽

1997 ◽

Vol 25 (5) ◽

pp. 497-503

Author(s):

Jean-Paul Morin ◽

Marc E. De Broe ◽

Walter Pfaller ◽

Gabriele Schmuck

Keyword(s):

Proximal Tubule ◽

Culture Media ◽

Task Force ◽

Primary Cultures ◽

Phenotypic Expression ◽

Transepithelial Transport ◽

Specific Cell ◽

Proximal Tubule Cells ◽

Tubule Cells

An ECVAM task force on nephrotoxicity has been established to advise, in particular, on the follow-up to recommendations made in the ECVAM workshop report on nephrotoxicity testing in vitro. Since this workshop was held, in 1994, there have been several improvements in the techniques used. For example, the duration of renal slice viability, and the maintenance of functional activities in slices, have been improved by using dynamic incubation systems with higher oxygen tensions and more-appropriate cell culture media. Highly differentiated primary cultures of pig, human and rabbit proximal tubule cells have been established by using specific cell isolation procedures and/or selective culture media. To date, the most comparable phenotypic expression and transepithelial transport capacities to proximal tubules in vivo have been obtained with primary cultures of rabbit proximal tubule cells which are grown on bicompartmental supports; in this system, transepithelial substrate gradients are generated and the transepithelial transport of both organic anions and cations is highly active. This in vitro system has been selected by ECVAM for further evaluation and prevalidation. Industrial needs in the area of nephrotoxicity testing have been identified, and recommendations are made at the end of this report concerning possible future initiatives.

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