サイトカインによるヒト近位尿細管細胞Kチャネル活性の調節

抄録

An inwardly rectifying K channel with inward conductance of 40 pS is the most frequently observed K channel in cultured human proximal tubule cells. We have previously reported that the activity of this K channel was modulated, at least in part, by nitric oxide (NO) which was mainly derived from inducible NO synthase (iNOS) in these cells. Since cytokines are known to enhance the expression of iNOS mRNA, we explored the effects of interleukin-1β (IL), tumor necrosis factor-α (TNF) and interferon-γ (IFN) on the K channel activity, using the patch-clamp technique and RT-PCR. After 24-h incubation of cells with each cytokine, iNOS mRNA was significantly increased by IFN (100 U/ml) but not by IL (10 U/ml) and TNF (200 U/ml). In cell-attached patches using the IFN-treated cells, a NOS substrate, L-arginine (500 μM) suppressed channel activity, whereas a NOS inhibitor, L-NAME (100 μM) stimulated it. These observations were in sharp contrast to the case with control cells where L-arginine was stimulatory and L-NAME was suppressive. Acute effects of cytokines on channel activity were tested in cell-attached patches using control cells. Addition of IL to the bath suppressed channel activity, which was not restored by the subsequent addition of L-arginine. On the other hand, addition of IFN stimulated channel activity and this stimulatory effect was not abolished by L-NAME. TNF had little effect on channel activity. These results suggested that IFN affected K channel activity through the NO-dependent and -independent pathways whereas the effect of IL was NO-dependent. [J Physiol Sci. 2006;56 Suppl:S81]