Structural studies of K+ channels and other ion channels have also indicated some general principles of how these channels open and close. The gating involves movement of the helices in the membrane so that they either obstruct or open the path for ion movement. Depending on the particular type of channel, helices tilt, rotate, or bend during gating. The structure of a closed K+ channel shows that by tilting the inner helices, the pore constricts like a diaphragm at its cytosolic end (Figure 11–26). Bulky hydrophobic amino acid side chains block the small opening that remains, preventing the entry of ions.
Many other ion channels operate on similar principles: the channel’s gating helices are allosterically coupled to domains that form the ion-conducting pathway; and a conformational change in the gate—in response, say, to ligand binding or altered membrane potential—brings about conformational change in the conducting pathway, either opening it or blocking it off.
All organisms, from single-cell bacteria to multicellular animals and plants, must sense and respond to mechanical forces in their external environment (such as sound, touch, pressure, shear forces, and gravity) and in their internal environment (such as osmotic pressure and membrane bending). Numerous proteins are known to be capable of responding to such mechanical forces, and a large subset of those proteins has been identified as possible mechanosensitive channels, but very few of the candidate proteins have been shown directly to be mechanically activated ion channels. One reason for this dearth in our knowledge is that most such channels are extremely rare. Auditory hair cells in the human cochlea, for example, contain extraordinarily sensitive mechanically gated ion channels, but each of the approximately 15,000 individual hair cells is thought to have a total of only 50–100 of them (Movie 11.9). Additional difficulties arise because the gating mechanisms of many mechanosensitive channel types require the channels to be embedded in complex architectures that require attachment to the extracellular matrix or to the cytoskeleton and are difficult to reconstitute in the test tube. The study of mechanosensitive receptors is a field of active investigation.
A well-studied class of mechanosensitive channels is found in the bacterial plasma membrane. These channels open in response to mechanical stretching of the lipid bilayer in which they are embedded. When a bacterium experiences a low-ionic-strength external environment (hypotonic conditions), such as
Figure 11–25 K+ specificity of the selectivity filter in a K+ channel. The drawings show K+ and Na+ ions (A) in the vestibule and (B) in the selectivity filter of the pore, viewed in cross section. In the vestibule, the ions are hydrated. In the selectivity filter, they have lost their water, and the carbonyl oxygens are placed to accommodate a dehydrated K+ ion. The dehydration of the K+ ion requires energy, which is precisely balanced by the energy regained by the interaction of the ion with all of the carbonyl oxygens that serve as surrogate water molecules. Because the Na+ ion is too small to interact with the oxygens, it can enter the selectivity filter only at a great energetic expense. The filter therefore selects K+ ions with high specificity. (A, adapted from Y. Zhou et al., Nature 414:43–48, 2001. With permission from Macmillan Publishers Ltd.)