Acute application of TNF stimulates apical 70-pS K⁺channels in the thick ascending limb of rat kidney

Abstract

. Acute application of TNF stimulates apical 70-pS K ϩ channels in the thick ascending limb of rat kidney. Am J Physiol Renal Physiol 285: F491-F497, 2003; 10.1152 10. /ajprenal.00104.2003 has been shown to be synthesized by the medullary thick ascending limb (mTAL) (21). In the present study, we used the patch-clamp technique to study the acute effect of TNF on the apical 70-pS K ϩ channel in the mTAL. Addition of TNF (10 nM) significantly stimulated activity of the 70-pS K ϩ channel and increased NPo [a product of channel open probability (Po) and channel number (N)] from 0.20 to 0.97. The stimulatory effect of TNF was observed only in cell-attached patches but not in excised patches. Moreover, addition of TNF had no effect on the ROMK-like small-conductance K ϩ channels in the TAL. The dose-response curve of the TNF effect yielded a Km value of 1 nM, a concentration that increased channel activity to 50% maximal stimulatory effect of TNF. The concentrations required for reaching the plateau of the TNF effect were between 5 and 10 nM. The stimulatory effect of TNF on the 70-pS K ϩ channel was observed in the presence of N -nitro-L-arginine methyl ester. This indicated that the effect of TNF was not mediated by a nitric oxidedependent pathway. Also, inhibition of PKA did not affect the stimulatory effect of TNF. In contrast, inhibition of protein tyrosine kinase not only increased activity of the 70-pS K ϩ channel but also abolished the effect of TNF. Moreover, inhibition of protein tyrosine phosphatase (PTP) blocked the stimulatory effect of TNF on the 70-pS K ϩ channel. The notion that the TNF effect results from stimulation of PTP activity is supported by PTP activity assay in which treatment of mTAL cells with TNF significantly increased the activity of PTP. We conclude that TNF stimulates the 70-pS K ϩ channel via stimulation of PTP in the mTAL.

Delayed and acute effects of interferon-γ on activity of an inwardly rectifying K+ channel in cultured human proximal tubule cells

“…However, little information is available regarding the effects of cytokines on K ϩ channel activity in renal tubular epithelia, excepting a report by Wei et al (31). They demonstrated that TNF acutely stimulated activity of an apical 70-pS K ϩ channel in the thick ascending limb of rat kidney (31). In the present study, we revealed that IFN-␥ possessed a delayed suppressive effect and an acute stimulatory effect on activity of the 40-pS K ϩ channel in cultured human proximal tubule cells.…”

“…However, there are few reports concerning the effects of cytokines on K ϩ channel activity in renal tubular cells. Until now, only Wei et al (31) reported that TNF stimulated activity of an apical 70-pS K ϩ channel in the thick ascending limb of rat kidney (31).…”

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

“…TNF-α is secreted by corneal epithelial cells in response to an inflammatory stimulation caused by bacterial and viral infections (Minami et al, 2002;Kurpakus-Wheater et al, 2003;Bitko et al, 2004;Kumar et al, 2004). TNF-α-stimulated increases in K + channel activities are important for TNF-α-induced cellular effects in cortical neurons, kidney epithelial cells, hepatic cells and corneal epithelial cells (Houzen et al, 1997;Nietsch et al, 2000;Wei et al, 2003). TNF-α also induces mRNA expression of various K + channel types during a systemic inflammatory response as well as tumor cell proliferation in brain and cancer cells Vicente et al, 2003Vicente et al, ,2004.…”

TNF-α promotes cell survival through stimulation of K+ channel and NFκB activity in corneal epithelial cells

“…On the other hand, UV irradiation also induces robust increases in channel activity in these cells, which in turn triggers apoptosis through activation of JNK signal cascades [20][21][22]. TNF-α-stimulated increases in K + channel activities are important for TNF-α-induced cellular effects in cortical neurons, kidney epithelial, and liver cells [23][24][25]. TNF-α also induces mRNA expression of various K + channel types during a systemic inflammatory response as well as tumor cell proliferation in brain and cancer cells [26][27][28].…”