Journal article

Publication year: 2014

Pages: 45-55

Journal: The FASEB Journal

Volume number: 28

Issue number: 1

ISSN: 0892-6638

eISSN: 1530-6860

DOI Link: https://doi.org/10.1096/fj.13-229252

Publisher: Wiley

Abstract: 
Lungs of air-breathing vertebrates are constantly exposed to mechanical forces and therefore are suitable for investigation of mechanotransduction processes in nonexcitable cells and tissues. Freshly dissected Xenopus laevis lungs were used for transepithelial short-circuit current (I-SC) recordings and were exposed to increased hydrostatic pressure (HP; 5 cm fluid column, modified Ussing chamber). I-SC values obtained under HP (I-5cm) were normalized to values before HP (I-0cm) application (I-5cm/I-0cm). Under control conditions, HP decreased I-SC (I-5cm/I-0cm=0.84; n=68; P<0.0001). This effect was reversible and repeatable 30 times. Preincubation with ATP-sensitive K+ channel (K-ATP) inhibitors (HMR1098 and glibenclamide) prevented the decrease in I-SC (I-5cm/I-0cm: HMR1098=1.19, P<0.0001; glibenclamide=1.11, P<0.0001). Similar effects were observed with hemichannel inhibitors (I-5cm/I-0cm: meclofenamic acid=1.09, P<0.0001; probenecid=1.0, P<0.0001). The HP effect was accompanied by release of ATP (P<0.05), determined by luciferin-luciferase luminescence in perfusion solution from the luminal side of an Ussing chamber. ATP release was abrogated by both meclofenamic acid and probenecid. RT-PCR experiments revealed the expression of pannexin and connexin hemichannels and K-ATP subunit transcripts in X. laevis lung. These data show an activation of K-ATP in pulmonary epithelial cells in response to HP that is induced by ATP release through mechanosensitive pannexin and connexin hemichannels. These findings represent a novel mechanism of mechanotransduction in nonexcitable cells.Richter, K., Kiefer, K. P., Grzesik, B. A., Clauss, W. G., Fronius, M. Hydrostatic pressure activates ATP-sensitive K+ channels in lung epithelium by ATP release through pannexin and connexin hemichannels.

Harvard Citation style: Richter, K., Kiefer, K., Grzesik, B., Clauss, W. and Fronius, M. (2014) Hydrostatic pressure activates ATP-sensitive K channels in lung epithelium by ATP release through pannexin and connexin hemichannels, The FASEB Journal, 28(1), pp. 45-55. https://doi.org/10.1096/fj.13-229252

APA Citation style: Richter, K., Kiefer, K., Grzesik, B., Clauss, W., & Fronius, M. (2014). Hydrostatic pressure activates ATP-sensitive K channels in lung epithelium by ATP release through pannexin and connexin hemichannels. The FASEB Journal. 28(1), 45-55. https://doi.org/10.1096/fj.13-229252