Hydrostatic pressure activates ATP‐sensitive K + channels in lung epithelium by ATP release through pannexin and connexin hemichannels

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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 + channel (K ATP ) inhibitors (HMR1098 and glibenclamide) prevented the decrease in I SC ( I 5cm / I 0cm : HMR1098=1.19, P P I 5cm / I 0cm : meclofenamic acid=1.09, P P P 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. FASEB J. 28, 45–55 (2014). www.fasebj.org

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