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First published online May 24, 2004
doi: 10.1242/10.1242/jcs.01232

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Mechanosensitive ion channels: molecules of mechanotransduction

School of Medicine and Pharmacology, QEII Medical Centre, University of Western Australia, Crawley, WA 6009, Australia

View larger version (27K): [in a new window]   Fig. 1. (A) Current traces for the Escherichia coli MscS and MscL channels recorded at a pipette voltage of +40 mV and +30 mV, respectively. C and On designate closed and open levels of n channels. (B) Boltzmann distribution curves for MscS and MscL. A Boltzmann distribution function of the form Po/1–Po=exp[(p–p1/2)] of the channel open probability Po plotted against suction p was calculated from the traces shown in A. (mmHg–1) is the slope of the plot ln[Po/(1–Po)] versus suction and describes the sensitivity to negative pressure of the channels, whereas p1/2 (mmHg) is the negative pressure at which Po equals 50% (1 mmHg=133 Pa). Adapted with permission from Elsevier (Martinac and Kloda, 2003). (C) Comparison of structures of the MscL and MscS channel. MscL forms homopentameric channels (Chang et al., 1998), whereas MscS is a homoheptamer (Bass et al., 2002). Colours indicating different structural elements are shown along the centerline of each channel molecule. Reproduced with permission from the American Association for the Advancement of Science (Bezanilla and Perozo, 2002). CYT, cytoplasmic region; TM, transmembrane region.

View larger version (42K): [in a new window]   Fig. 2. (A) Structure of the MscL channel in the open state viewed from the extracellular side. (B) Side views of the transmembrane domains TM1 and TM2 of the open channel. The inset shows the structure of the channel monomer. Modified with permission from Nature (Perozo et al., 2002a). (C) Assymetry of the tension gradient across the lipid bilayer is required for MscL opening. Changes in the spectral line shape from position Ile24 obtained by the EPR spectroscopy were used to monitor the influence of different bilayer tension gradients produced by different lipid environments on the conformation of MscL: symmetric phosphatidylcholine (PC18; closed), asymmetric lysophosphatidylcholine (LPC; open), detergent solution (closed), and symmetric LPC (closed). Note, narrowing of the spectral line after addition of LPC to one monolayer indicates a large increase in spin probe mobility together with complete elimination of any intersubunit spin-spin interaction, which is characteristic of the open channel. Reproduced with permission from Nature (Perozo et al., 2002b).

View larger version (17K): [in a new window]   Fig. 3. (A) Boltzmann distribution curves for MscMJ () and MscMJLR () from Methanococcus jannashii. See legend of Fig. 1 for details [adapted with permission from Elsevier (Martinac and Kloda, 2003)]. (B) Structural models of MscMJ and MscMJLR monomers based on the MscS crystal structure, generated by Swiss-Model (Guex and Peitsch, 1997) and viewed by PyMol (PyMOL + AMBER Trajectories, Vanderbilt University Center for Structural Biology; http://structbio.vanderbilt.edu/archives/amber-archive/2002/1207.phtml).

View larger version (26K): [in a new window]   Fig. 4. (A) MscL subfamily of bacterial MS channels. (B) Phylogenetic tree of MscS homologues. Bacterial MS channels are shown in black, archaeal channels are shown in red, homologues found in fungi and plants are shown in green. The homologues were retrieved from the existing databases (GenBank, Protein DataBank and SwissProt) using BLAST (Altschul et al., 1997) [adapted with permission from Elsevier (Martinac and Kloda, 2003)].

View larger version (34K): [in a new window]   Fig. 5. (A) Organization of two-pore-domain (2P-domain) K+ channels. P1 and P2 refer to the pore region in the channel monomer. (B) Activation of TREK by membrane stretch is pH dependent and follows a sigmoidal relationship. NPo denotes open probability of N number of TREK channels in the patch. For details see text. (Courtesy of E. Honoré.)

View larger version (26K): [in a new window]   Fig. 6. A model of the MS channel from Caenorhabditis elegans. (A) The channel is formed from five subunits, including the MEC-4, MEC-6 and MEC-10 membrane proteins, and the integral membrane protein MEC-2, which is homologous to stomatin (a red blood cell protein that binds to the cytoskeleton and regulates cation conductance). In the model, MEC-2 connects the MS channel to microtubules (composed of - and ß-tubulin encoded by mec-12 and mec-7, respectively). (B) The MEC-1 and MEC-5 (a unique collagen) proteins make the mantle, whose pushing by the shearing force F (arrow) results in opening of the MS channel. MEC-9 is an extracellular protein, which does not form the mantle, but is proposed to form the gating spring between the MS channel and the mantle. Figure reproduced with permission from Elsevier (Hamill and McBride, 1996a).