Abstract
The proximal tubule reabsorbs about 70% of the filtered Na+ load. The K+ channels in proximal tubule cells contribute to this process through the formation of the membrane potential, which serves as a driving force for electrogenic passive transport of Na+. In cultured human proximal tubule cells, an inwardly rectifying K+ channel with an inward conductance of 40 pS is the most frequently observed K+ channel under the control condition. We previously reported that nitric oxide (NO) possessed a dose-dependent biphasic effect on this K+ channel, i.e. a cGMP/PKG-dependent stimulatory effect at low doses and a nitrosylation-dependent suppressive effect at high doses. We also confirmed that interferon-γ (IFN) chronically suppressed the K+ channel activity by enhancing expression of inducible NO synthase (iNOS). In this study, we examined whether IFN would acutely affect the activity of the 40 pS K+ channel, using the patch-clamp technique. In cell-attached patches, IFN (20 ng/ml) added to the bath increased channel activity within 1-3 min. IFN had no effect on channel activity in inside-out patches. The acute stimulatory effect of IFN was not abolished by a NOS inhibitor, L-NAME (100 μM), an inhibitor of soluble guanylate cyclase, ODQ (10 μM), or a PKG inhibitor, KT5823 (1 μM). On the other hand, a tyrosine kinase inhibitor, genistein (100 μM), reduced the stimulatory effect of IFN. These results suggested that IFN acutely stimulated K+ channel activity through activation of tyrosine kinases, but not through the NO/cGMP/PKG pathway. [J Physiol Sci. 2007;57 Suppl:S85]
