Crystal structure of the MthK Ca2+-regulated K+ channel from the archaeon Methanobacterium thermoautotrophicum, a thermophilic microbe. The view is from the extracellular side of the channel in the Ca2+-bound open state. MthK consists of two major functional domains. An integral membrane protein forms an aqueous pore (blue), which selects and conducts K+ ions, and has a gate that switches between open and closed conformations; an intracellular Ca2+-binding gating ring (gray) controls the gate. When it binds Ca2+, the resulting conformational change is mechanically transmitted to the pore, causing it to switch to the open state. (Used with permission of Kenton Swartz, based on PDB code 1LNQ, from Jian Y, Lee A, Chen J, et al. 2002. Nature 417:523–526.)
IN ALL BIOLOGICAL SYSTEMS, FROM THE MOST primitive to the most advanced, the basic building block is the cell. Cells are often organized into functional modules that are repeated in complex biological systems. The vertebrate brain is the most complex example of a modular system. Complex biological systems have another basic feature: They are architectonic—that is, their anatomy, fine structure, and dynamic properties all reflect a specific physiological function. Thus, the construction of the brain and the cell biology, biophysics, and biochemistry of its component cells reflect its fundamental function, which is to mediate behavior.
The nervous system is made up of glial cells and nerve cells. Earlier views of glia as purely structural elements have been supplanted by our current understanding that there are several types of glial cells, each of which is specialized to regulate one or more particular aspects of neuronal function. Different varieties of glial cells play essential roles in enabling and guiding neural development, insulating axonal processes, controlling the extracellular milieu, supporting synaptic transmission, facilitating learning and memory, and modulating pathological processes within the nervous system. Some glial cells have receptors for neurotransmitters and voltage-gated ion channels that enable them to communicate with one another and with neurons to support neuronal signaling.
In contrast to glial cells, the great diversity of nerve cells—the fundamental units from which the modules of the nervous systems are assembled—are variations on one basic cell plan. Four features of this plan give nerve cells the unique ability to communicate with one another precisely and rapidly over long distances. First, the neuron is polarized, possessing receptive dendrites on one end and communicating axons with presynaptic terminals at the other. This polarization of functional properties restricts the predominant flow of voltage impulses to one direction. Second, the neuron is electrically excitable. Its cell membrane contains specialized proteins—ion channels and receptors—that permit the influx and efflux of specific inorganic ions, thus creating electrical currents that generate the voltage signals across the membrane. Third, the neuron contains proteins and organelles that endow it with specialized ...