Mechanosensitive channel

Sukharev, S. and Corey, D. P. Mechanosensitive channels multiplicity of families and gating paradigms. Sci. STKE... 

The molecular nature of the neuronal receptors is now becoming understood with the advent of molecular biological techniques. The molecular structure of the mechanosensitive channels has been established only recently. In principle mechanosensitive channels must be opened by mechanical deformation of the neural membrane in which they are em-... 

S. Sukharev and A. Anishkin. Mechanosensitive channels what can we learn from simple model systems TINS 27(6), 2004. 

Mechanosensitive ion channels can be looked at as membrane-embedded mechano-electrical switches. They play a critical role in transducing physical stresses at the cell membrane (e.g. lipid bilayer deformations) into an electrochemical response. Two types of stretch-activated channels have been reported the mechanosensitive channels of large conductance (MscL) and mechanosensitive channels of small conductance (MscS). 

Sukharev, S. (1999). Mechanosensitive channels in bacteria as membrane tension reporters, FASEB J., 13 (Suppl.), S55-S61. 

Bass, R. B., Strop, P., Barclay, M. and Rees, D. C. (2002). Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel, Science, 298, 1582-1587. 

Figure 2. A proposed model demonstrating several different prominent calcium-related pathways whose activity may be altered in dystrophic muscle. Increased activity of mechanosensitive channels (MS) and store-activated channels (SOC), which are likely derived from the same gene product (TRPC), and the calcium leak channel, which could represent a proteolyzed TRPC SOC channel. Decreased mechanical coupling between L-type VGCC and ryanodine receptors may increase basal calcium release from calcium stores (not shown). Further, increased IP, and IP, receptor levels may also enhance basal and stimulated calcium-induced calcium release (CICR) from calcium stores. Calcium store depletion can increase translocation of SOCs from intracellular vesicles to the sarcolemma. Finally, the relationship between increased membrane fragility and tearing is less certain, but calcium influx through sarcolemmal tears could lead to calcium-dependent proteolysis and increased activity of calcium leak channels, as well as proteolysis of other targets, and increased release of calcium from intracellular stores through CICR. This model is not meant to be comprehensive, and other calcium-related molecules are discussed in the text...

Franco-Obregon, A., and Lansman, J.B., 2002, Changes in mechanosensitive channel gating following mechanical stimulation in skeletal muscle myotubes from the mdx mouse, J Physiol, 539, pp 391-407. 

McBride, D.W., Jr., and Hamill, O.P., 1992, Pressure-clamp a method for rapid step perturbation of mechanosensitive channels, Pflugers Arch, 421, pp 606-612. 

Cui, C., Smith, D.O. and Adler, J. (1995) Characterization of mechanosensitive channels in Eschericia cofi cytoplasmic cell membrane by whole-cell patch clamp recording. Journal of Membrane Biology 144 31-42... 

Sackin, H. (1995) Mechanosensitive channels. Annual Review of Physiology 57 333-353... 

Mechanosensitive channels respond to changes in membrane tension. A prokaryotic large-conductance mechanosensitive channel, MscL, opens in response to osmotic stress to form a water filled channel between 3 and 4 nm across [18]. The change in pressure on the bilayer imparts a small movement in a transmembrane helix that is then followed by a dramatic rearrangement of the transmembrane domain to a fully open state. 

Perozo E et al (2002) Open channel structure of MscL and the gating mechanism of mechanosensitive channels. Nature 418 942-948... 

Fig. 1. Predicted membrane-spanning topology for mechanosensitive channels found in eukaryotes (TRPV, K2P, and DEG/ENaC channels) and bacteria (MscL and MscS). In addition to the transmembrane helices (represented as cylinders), other motifs present in these channels are designated as follows. The TRPV channels contain several cytoplasmic ankyrin domains (A) at the N terminus, and one pore-forming loop (P). K2P channels have two pore-forming loops and a self-interaction domain (SID) through which dimers are generated. DEG/ENaC sodium channels have a single pore-forming loop and three cysteine-rich domains (CRDs).

In this review, we first introduce some general background considerations relevant to the description of mechanosensitive channels, followed... 

The consequences of applied membrane tension to an intrinsically mechanosensitive channel can be readily evaluated for a simple two-state system where the channel can exist in either closed (C) or open (O) conformations ... 

The steepness of the response of the channel to applied tension is determined by the magnitude of the change in cross-sectional area for example, in terms of units typically employed in these calculations, if AA= 100 A2, then an increase of 1 dyn cm 1 in membrane tension corresponds to a free energy change of —0.602 kj/mol, and AG will scale proportionally to changes in A A. Consequently, for a channel with A G° = 40 kj/mol and crj/2 = 10 dyn cm-1 (typical for mechanosensitive channels such as MscL), AA 660 A2. 

Owing to the pioneering efforts of C. Kung, the best characterized mechanosensitive channel is the prokaryotic MscL, the mechanosensitive channel of large conductance. MscL was originally identified, isolated, and characterized by Kung and co-workers using a biochemical approach in combination with a patch-clamp assay to isolate an intrinsically stretch activated channel from E. coli membranes (Sukharev et al.,... 

The possibility that changes in bilayer curvature might be implicated in the gating of mechanosensitive channels was motivated by the observation that addition of amphiphiles to one side of the membrane can... 

A third mechanosensitive channel of mini conductance (MscM) has been functionally identified in E. coli (Berrier et al., 1989, 1996), although the encoding gene has not yet been reported. This channel has a conductance of less than half that of MscS (0.1—0.4 nS), with slow opening/closing kinetics relative to MscS, and especially MscL (Berrier et al., 1993). In contrast to MscL and MscS, MscM has pronounced cation selectivity. 

---