exact balance of charges on each side of the a few of the positive ions (red) cross the membrane; membrane potential = 0 membrane from right to left, leaving their small direct contribution to the membrane potential by pumping out three Na+ for every two K+ that it pumps in (see Figure 11–15). However, switching off the pump does not abolish the major component of the resting potential, which is generated by the K+ equilibrium mechanism just described. This component of the membrane potential persists as long as the Na+ concentration inside the cell stays low and the K+ ion concentration high—typically for many minutes. But the plasma membrane is somewhat permeable to all small ions, including Na+. Therefore, without the Na+-K+ pump, the ion gradients set up by the pump will eventually run down, and the membrane potential established by diffusion through the K+ leak channels will fall as well. As Na+ enters, the cell eventually comes to a new resting state where Na+, K+, and Cl– are all at equilibrium across the membrane. The membrane potential in this state is much less than it was in the normal cell with an active Na+-K+ pump.
The resting potential of an animal cell varies between –20 mV and –120 mV, depending on the organism and cell type. Although the K+ gradient always has a major influence on this potential, the gradients of other ions (and the disequilibrating effects of ion pumps) also have a significant effect: the more permeable the membrane for a given ion, the more strongly the membrane potential tends to be driven toward the equilibrium value for that ion. Consequently, changes in a membrane’s permeability to ions can cause significant changes in the membrane potential. This is one of the key principles relating the electrical excitability of cells to the activities of ion channels.
To understand how ion channels select their ions and how they open and close, we need to know their atomic structure. The first ion channel to be crystallized and studied by x-ray diffraction was a bacterial K+ channel. The details of its structure revolutionized our understanding of ion channels.
The Three-Dimensional Structure of a Bacterial K+ Channel Shows How an Ion Channel Can Work
Scientists were puzzled by the remarkable ability of ion channels to combine exquisite ion selectivity with a high conductance. K+ leak channels, for example, conduct K+ 10,000-fold faster than Na+, yet the two ions are both featureless spheres and have similar diameters (0.133 nm and 0.095 nm, respectively). A single amino acid substitution in the pore of an animal cell K+ channel can result in a loss of ion selectivity and cell death. We cannot explain the normal K+ selectivity by pore size, because Na+ is smaller than K+. Moreover, the high conductance rate is incompatible with the channel’s having selective, high-affinity K+-binding sites, as the binding of K+ ions to such sites would greatly slow their passage.
The puzzle was solved when the structure of a bacterial K+ channel was determined by x-ray crystallography. The channel is made from four identical trans-membrane subunits, which together form a central pore through the membrane. Each subunit contributes two transmembrane α helices, which are tilted outward in the membrane and together form a cone, with its wide end facing the outside of