Objective: 

Due to the breathing movements, the pulmonary epithelium is permanently exposed to mechanical forces (e.g. shear force and stretch). Among other effects there is evidence that distention of pulmonary epithelia leads to an activation of ATP-sensitive K⁺ (K_ATP) channels (Bogdan et al. 2008). The aim of the present study was to clarify the mechanisms of K_ATP channel activation and the contribution of hemichannels in particular.

Methods: 

Freshly dissected pulmonary epithelial preparations from Xenopus laevis lungs were used for Ussing-chamber recordings. The used Ussing-chamber enabled the application of hydrostatic pressure (HP) in order to mechanically stimulate the tissue while the short-circuit current (I_SC) was recorded. As a K_ATP channel inhibitor HMR1098 was used. The contribution of hemichannels was tested by meclofenamic-acid and probenecid.

Results: 

HMR1098 prevented the HP-induced current decrease that is due to the activation of apical localized K_ATP channels. Interestingly, the HP-induced inhibition of the I_SC was also prevented by the connexin hemichannel blocker meclofenamic-acid (0.1 mM) as well as by the pannexin hemichannel inhibitor probenecid (1 mM).

Conclusion: 

K_ATP channels are activated by HP. Since the HP-induced K_ATP channel activation is inhibited by hemichannel inhibitors, we hypothesize that HP induces an ATP-release via mechanosensitive connexin and pannexin hemichannels. Hemichannel activation and the release of ATP via these channels leads to the activation of K_ATP channels as observed. Further, this study demonstrates that ion transport and therefore fluid balance by pulmonary epithelia is mediated by mechanical forces as appearing under normal breathing conditions.