Journal
CELL CALCIUM
Volume 45, Issue 1, Pages 55-64Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2008.06.002
Keywords
Signaling; Second messenger; SACs; SIAs; NAD(P)H oxidase
Categories
Funding
- Deutsche Forschungsgemeinschaft [TR02, Is24-19/1]
- Medical Faculty Halle [12/19]
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In murine ventricular myocytes, activation of mechanosensitive ion channels (MSCs) includes activation of non-selective cation currents and deactivation of inwardly rectifying potassium currents. Using pharmacological inhibitors and knockout models, we analyzed signaling steps that are critical to transduce the mechanical signal (stretch) into etectrophysiological events (MSC). We provide evidence for an activation of NAD(P)H oxidase and NOS3 in response to stretch putatively via the angiotensin 11 receptor type 1. The involvement of superoxide and nitric oxide was verified by the block of MSC using specific scavengers (tiron and PTIO, respectively). Superoxide and nitric oxide are known to combine very rapidly to form peroxynitrite. Accordingly, MSC were blocked by the peroxynitrite scavenger uric acid and could be mimicked by application of exogenous peroxynitrite. Peroxynitrite formation may activate phospholipases generating amphipaths that modulates channel function via changing the curvature of the surrounding lipid bilayer. This conclusion is supported by our findings that MSC were suppressed by inhibitors of phospholipases but could be mimicked by exogenous phospholipases or by amphipaths (oleic acid, Triton X-100). (C) 2008 Elsevier Ltd. All rights reserved.
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