Erratum to: Role of Calcineurin-Mediated Dephosphorylation in Modulation of an Inwardly Rectifying K+ Channel in Human Proximal Tubule Cells

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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Constitutive Activity of Inwardly Rectifying K+ Channel at Physiological [Ca]i Is Mediated by Ca2+/CaMK II Pathway in Opossum Kidney Proximal Tubule Cells

The Journal of Physiological Sciences ◽

10.2170/physiolsci.rp014507 ◽

2008 ◽

Vol 58 (3) ◽

pp. 199-207 ◽

Cited By ~ 1

Author(s):

Yoshiaki Mori ◽

Hideyo Yoshida ◽

Manabu Miyamoto ◽

Yoshiro Sohma ◽

Takahiro Kubota

Keyword(s):

Proximal Tubule ◽

K Channel ◽

Constitutive Activity ◽

Proximal Tubule Cells ◽

Opossum Kidney ◽

Kidney Proximal Tubule ◽

Tubule Cells ◽

Inwardly Rectifying

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Role of MAPK pathways in light chain-induced cytokine production in human proximal tubule cells

AJP Renal Physiology ◽

10.1152/ajprenal.00350.2002 ◽

2003 ◽

Vol 284 (6) ◽

pp. F1245-F1254 ◽

Cited By ~ 55

Author(s):

Sule Sengul ◽

Craig Zwizinski ◽

Vecihi Batuman

Keyword(s):

Proximal Tubule ◽

Light Chain ◽

Cytokine Production ◽

Tubulointerstitial Injury ◽

Proximal Tubule Cells ◽

Mapk Pathways ◽

Cytokine Responses ◽

Tubule Cells ◽

Human Proximal Tubule

We previously demonstrated that light chain (LC) endocytosis by human proximal tubule cells (PTCs) leads to production of cytokines through activation of NF-κB. Here, we examined the role of MAPK pathways in these responses using four species of myeloma LCs (κ1, κ2, κ3, and λ1) previously shown to induce cytokine production by PTCs. Among these, κ1-LC, which yielded the strongest cytokine responses, was selected for detailed studies. Activation of MAPKs was probed by Western blot analysis for the active kinases, ERK 1/2, JNK 1/2, and p38 in κ1-LC-exposed human PTCs. To evaluate the functional role of MAPKs in LC-induced cytokine responses, we tested the effects of U-0126, an ERK inhibitor; SP-600125, an inhibitor of JNK; SB-203580, a p38 inhibitor; and curcumin, a JNK-AP-1 inhibitor, all added to media before 4-h exposure to 1.5 mg/ml κ1-LC. IL-6 and monocyte chemotactic protein-1 (MCP-1) were determined by ELISA. Both LC and human serum albumin (HSA) activated ERK, although the HSA effect was weaker. κ1-LC stimulated all three MAPKs, although phosphorylation of ERK was more pronounced and sustained than others. Inhibitors of ERK, JNK, and p38 reduced LC-induced IL-6 and MCP-1 production. These findings suggest that activation of MAPKs plays a role in LC-induced cytokine responses in PTCs. Activation of MAPKs may be involved in cytokine responses induced by other proteins as well as LCs and may be pivotal in the pathophysiology of tubulointerstitial injury in proteinuric diseases.

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