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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
MECHANOSENSITIVE ATP-RELEASE TROUGH PANNEXIN AND CONNEXIN HEMICHANNELS INVOLVES ACTIVATION OF ATP-SENSITIVE K+ CHANNELS IN NATIVE PULMONARY EPITHELIUM (XENOPUS LAEVIS)
Abstract number: P258
Richter
1
*K.
, Kiefer
1
K.P., Lintges
1
M., Geissert
1
L., Bender
1
N., Clauss
1
W., Fronius
1
M.
1
Justus-Liebig-University Giessen, Institut of Animal Physiology, Gießen, Germany
Question:
Due to the breathing movements pulmonary epithelia are permanently exposed to mechanical forces (e.g. shear force and stretch). Among other effects there is preliminary evidence that distention of alveolar epithelium activates ATP-sensitive K+ (KATP) channels. The aim of this study was to reveal the mechanisms of KATP channel activation.
Methods:
A modified Ussing-chamber that enabled the application of hydrostatic pressure (HP) was used to mechanically stimulate native pulmonary epithelia of Xenopus laevis lungs while the short-circuit current (ISC) was recorded. To clarify the mechanosensitive activation of KATP channels the specific inhibitor HMR1098 was used. Contribution of hemichannels in this process was tested with connexin (meclofenamic-acid) and pannexin (probenecid) hemichannel inhibitors. Further samples of the out flowing perfusate were collected for determination of extracellular ATP-levels via a luminescence ATP detection assay.
Results:
Transcripts encoding for the KATP channel subunit Kir6.1 and SUR1 were detected by Reverse Transcriptase (RT)-PCR. Apical application of HP led to a pressure-induced current decrease (~16%; n=68; pATP channel inhibitor HMR 1098 (60 µM) prevented the HP-induced effect. The HP-induced effect was also prevented by hemichannel inhibitors (probenecid, meclofenamic acid). The expression of pannexin and connexin hemichannels was revealed in RT-PCR experiments. Further, the HP-induced effect was accompanied by increased ATP concentrations in the extracellular solution (control) that was inhibited by the hemichannel inhibitors.
Conclusion:
These data indicate that KATP channel activation of pulmonary epithelial cells in response to HP is induced by ATP release through mechanosensitive hemichannels.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P258