Mechanosensitive ion channels

Mechanosensitive (MS) ion channels are to date the best characterized biological force-sensing systems. They present the best example of coupling protein conformations to the mechanics of the surrounding cell membrane. Studies of MS channels conducted over the last 28 years have from their serendipitous discovery and confusion about their artifactual nature to their molecular identification and structural determination greatly contributed to our understanding of molecular mechanisms underlying the physiology of mechanosensory transduction. Mechanotransduction is ancient, dating back some 3.8 billion years when the first life forms appeared of which microbes form the largest group. Diversity, number and adaptability of microbial cells enabled them to populate all kinds of environments supporting life. Mechanical forces primordial cells must have sensed and responded to first resulted predominantly from osmotic pressure intrinsically linked to the essential role that water plays for the existence of life. MscL and MscS channels, whose discovery in bacteria coincided inherently with the advent of the patchclamp technique, serve today as a paradigm for mechanosensory transduction. They are currently the best biophysical models used to study molecular principles of mechanosensory transduction. Their primary function is that of emergency valves releasing excess osmolytes upon hypo-osmotic stress to which bacterial cells become exposed in their living environments. In cells and tissues of eukaryotes, MS ion channels were first documented in patch clamp experiments by exposing membrane patches of red blood cells to hypotonic shock or by applying negative pressure to membrane patches of frog muscle and chick skeletal muscle cells. Despite much electrophysiological information, molecular characterization of the MS channel role in mechanotransduction in eukaryotes has been slow compared with the progress made in the research on bacterial MS channels. This is because of the experimental advantages bacteria offer for molecular biological, biochemical and structural work, which greatly facilitated the cloning and crystallization of bacterial MS channels. The crystal structure of the human MS ion channel TRAAK, a member of the two pore domain K+ channel family controlling the resting membrane potential in neuronal cells, has only very recently been solved and reported. In animals and humans, MS ion channels function as molecular transducers of mechanical stimuli in senses of hearing and touch, blood pressure and cell volume regulation, as well as Mechanosensitive ion channels An evolutionary and scientific tour de force in mechanobiology