Effects of cytokines on potassium channels in renal tubular epithelia

Abstract

Renal tubular potassium (K(+)) channels play important roles in the formation of cell-negative potential, K(+) recycling, K(+) secretion, and cell volume regulation. In addition to these physiological roles, it was reported that changes in the activity of renal tubular K(+) channels were involved in exacerbation of renal cell injury during ischemia and endotoxemia. Because ischemia and endotoxemia stimulate production of cytokines in immune cells and renal tubular cells, it is possible that cytokines would affect K(+) channel activity. Although the regulatory mechanisms of renal tubular K(+) channels have extensively been studied, little information is available about the effects of cytokines on these K(+) channels. The first report was that tumor necrosis factor acutely stimulated the single channel activity of the 70 pS K(+) channel in the rat thick ascending limb through activation of tyrosine phosphatase. Recently, it was also reported that interferon-γ (IFN-γ) and interleukin-1β (IL-1β) modulated the activity of the 40 pS K(+) channel in cultured human proximal tubule cells. IFN-γ exhibited a delayed suppression and an acute stimulation of K(+) channel activity, whereas IL-1β acutely suppressed the channel activity. Furthermore, these cytokines suppressed gene expression of the renal outer medullary potassium channel. The renal tubular K(+) channels are functionally coupled to the coexisting transporters. Therefore, the effects of cytokines on renal tubular transporter activity should also be taken into account, when interpreting their effects on K(+) channel activity.

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“…In addition, the major fraction of sodium is reabsorbed at the kidney proximal tubule by Na,K-ATPase, apical type 3 Na/H exchanger (NHE3) and Na-K-2Cl cotransporter (NKCC2) [ 6 ]. During endotoxemia, proximal tubular cells, the primary target of endotoxemia, develop abnormal expression or distribution of sodium transporters, leading to impaired sodium reabsorption [ 8 ]. A marked decrease of Na,K-ATPase, NHE3 and NKCC2 has been observed in endotoxemic animals [ 4 , 9 ], further indicating that dysregulation of sodium transporters may be closely related to abnormal proximal tubular sodium reabsorption.…”

Autoimmune Disease pH and Temperature

“…Could interferon possibly be impacting the cellular pumps, channels, transporters and isoenzymes? yes, it is known to impact the potassium channels for example [5]. Finally, if pH changes enough there could be a charge generated which could impact movement possibly even for T and B cells.…”