Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 295, Issue 4, Pages F1052-F1062Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00031.2008
Keywords
microdissected renal tubules; whole-cell patch-clamp recording; serine proteases; epithelial sodium transport; amiloride
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Funding
- Deutsche Forschungsgemeinschaft [SFB423, TP-A12]
- Deutsche Nierenstiftung
- International Society of Nephrology fellowship
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Proteases are involved in the processing and activation of the epithelial sodium channel (ENaC). The aim of the present study was to investigate whether the prototypical serine protease trypsin can activate ENaC in microdissected, split-open mouse renal distal tubules. Whole-cell patch-clamp recordings from principal cells of connecting tubules (CNT) or cortical collecting ducts (CCD) demonstrated that addition of trypsin (20 mu g/ml) to the bath solution increased the ENaC-mediated amiloridesensitive whole cell current (Delta I-Ami) in the majority of cells. In contrast, trypsin applied in the presence of an excess of soybean trypsin inhibitor had no stimulatory effect. The Delta I-Ami response to trypsin was variable, ranging from no apparent effect to a twofold increase in Delta I-Ami with an average stimulatory effect of 31 or 37% in mice on low-Na+ or standard Na+ diet, respectively. In cultured M-1 mouse collecting duct cells, a robust stimulatory effect of trypsin on Delta I-Ami was only observed in cells pretreated with protease inhibitors. This suggests that endogenous proteases contribute to ENaC activation in renal tubular cells and that the degree of ENaC prestimulation by endogenous proteases determines the magnitude of the stimulatory response to exogenous trypsin. In conclusion, we provide electrophysiological evidence that trypsin can stimulate ENaC activity in native renal mouse tubules. Thus, in the kidney, ENaC stimulation by extracellular proteases may be a relevant regulatory mechanism in vivo.
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