Abstract
The bacterial MscL (mechanosensitive channel of large conductance) is one of the best studied Mechanosensitive (MS) channels owing to its resolved 3D structure by X-ray crystallography. In addition MscL is known to be activated solely by tension in the membrane and a tension sensitive region of MscL has been determined. However, how tension leads to structural changes towards channel opening remains to be solved, mainly because we do not know the precise profile of tension generation during membrane stretch. To address this issue, we investigated the effects of the membrane perturbing amphipath chlorpromazine (CPZ) on the MscL activation using the patch-clamp technique. CPZ is known to be an MS channel activator that is supposed to preferentially insert in the inner leaflet of the lipid bilayer. Application of micromolar concentrations of CPZ decreased the threshold tension to activate MscL in a dose-dependent manner resulting in a leftward shift of the open probability vs. tension curve. It is suggested that CPZ systematically modifies tension profile in the bilayer, thus could be a useful tool to explore the biophysical mechanism of MscL activation by membrane tension. [J Physiol Sci. 2008;58 Suppl:S85]
