The function of the lung is in many aspects regulated by mechanical stimuli. To investigate the effect of mechanical forces on a native lung preparation we used excised lungs of Xenopus laevis and recorded the transepithelial short circuit current (Isc ) in Ussing-chamber measurements. Mechanical stress was induced by applying hydrostatic pressure to the apical side of the tissue. This procedure decreased Isc within several minutes by approximately 20% (n=152). The pressure-induced inhibition (Ip) was partly due to K+ secretion as the effect was reduced when extracellular K+ concentration was elevated or when K+ channels were blocked with Ba2+ or clotrimazole. In parallel a Cl- secretion was induced which could be inhibited by NFA or DIDS. Further on Ip was dependent on solution osmolarity and could be inhibited with Gd3+ and La3+ , both known blockers of mechanosensitive channels. RT-PCR revealed the presence of the osmotically regulated channel TRPV4 as well as the mechanosensitive channel TRPC1 in whole organ RNA isolation. The results suggest, that hydrostatic pressure has an impact on ion transport in native lung preparations including an activation of K+ and Cl- channels and presumably mechanosensitive channels. All these features exhibit similarities to cell volume regulatory mechanisms.

Supported by DFG, FR2124