Na+, Ca2+, or Cl– ions. These channels are also impermeable to H+, which is mainly present in cells as H3O+. These hydronium ions diffuse through water extremely rapidly, using a molecular relay mechanism that requires the making and breaking of hydrogen bonds between adjacent water molecules (Figure 11–20C). Aquaporins contain two strategically placed asparagines, which bind to the oxygen atom of the central water molecule in the line of water molecules traversing the pore, imposing a bipolarity on the entire column of water molecules (Figure 11–20C and D). This makes it impossible for the “making and breaking” sequence of hydrogen bonds (shown in Figure 11–20C) to get past the central asparagine-bonded water molecule. Because both valences of this central oxygen are unavailable for hydrogen-bonding, the central water molecule cannot participate in an H+ relay, and the pore is therefore impermeable to H+.
We now turn to ion channels, the subject of the rest of the chapter.
Two important properties distinguish ion channels from aqueous pores. First, they show ion selectivity, permitting some inorganic ions to pass, but not others. This suggests that their pores must be narrow enough in places to force permeating ions into intimate contact with the walls of the channel so that only ions of appropriate size and charge can pass. The permeating ions have to shed most or all of their associated water molecules to pass, often in single file, through the narrowest part of the channel, which is called the selectivity filter; this limits their rate of passage (Figure 11–21). Thus, as the ion concentration increases, the flux of the ion through a channel increases proportionally but then levels off (saturates) at a maximum rate.
Figure 11–20 The structure of aquaporins. (A) A ribbon diagram of an aquaporin monomer. In the membrane, aquaporins form tetramers, with each monomer containing an aqueous pore in its center (not shown). Each individual aquaporin channel passes about 109 water molecules per second. (B) A longitudinal cross section through one aquaporin monomer, in the plane of the central pore. One face of the pore is lined with hydrophilic amino acids, which provide transient hydrogen bonds to water molecules; these bonds help line up the transiting water molecules in a single row and orient them as they traverse the pore. (C and D) A model explaining why aquaporins are impermeable to H+.
(C) In water, H+ diffuses extremely rapidly by being relayed from one water molecule to the next. (D) Carbonyl groups (C=O) lining the hydrophilic face of the pore align water molecules, and two strategically placed asparagines in the center help tether a central water molecule such that both valences on its oxygen are occupied. This arrangement bipolarizes the entire line of water molecules, with each water molecule acting as a hydrogen-bond acceptor from its inner neighbor (Movie 11.6). (A and B, adapted from R.M. Stroud et al., Curr. Opin. Struct. Biol. 13:424–431, 2003. With permission from Elsevier.)
Figure 11–21 a typical ion channel, which fluctuates between closed and open conformations. The ion channel shown here in cross section forms a pore across the lipid bilayer only in the “open” conformational state. The pore narrows to atomic dimensions in one region (the selectivity filter), where the ion selectivity of the channel is largely determined. Another region of the channel forms the gate.
Figure 11–22 The gating of ion channels. This schematic drawing shows several kinds of stimuli that open ion channels. Mechanically gated channels often have cytoplasmic extensions (not shown) that link the channel to the cytoskeleton.