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After studying this chapter, the student should be able to:

  • Understand the structure and barrier properties of neural membranes.

  • Understand how protein complexes form channels in membranes that selectively permit ion movement through the membrane.

  • Know how active transporters create concentration balances for different ions.

  • See how the Nernst potential equates diffusional force with electrical force on various ions.

  • Understand the operation (gating) of various ion channels and their role in the electrical activity of neurons.


Although the plasma membrane is necessary for maintaining the integrity of neurons (and glial cells) by providing a barrier that keeps the cytoplasmic cellular contents separated from the extracellular space, it is also an essential element upon which all electrical signaling is based. The insulator properties of this thin lipid bilayer allow for the development of a transmembrane potential, but also impede the very movement of ions (along with other molecules) needed to establish ionic concentration gradients across the membrane, the central foundation of electrical excitability. To overcome the impermeability of the membrane to ions, complex membrane-spanning protein structures have evolved to form both ion channels and membrane exchangers, transporters, and pumps, which allow for the selective passage of ions across the bilayer. This chapter will discuss the lipid bilayer, ion channels, and various transmembrane ionic carrier systems.

Phospholipids, Fatty Acids, & Lipid Bilayers

The chief constituents of membranes are the amphipathic phospholipid molecules (>50%), which contain both a hydrophilic phosphate-containing polar head group and a pair of fatty acid chain tails. Some of the most common phospholipids are phosphatidylcholine, phosphatidylserine, and phosphatidyl ethanolymine. In the watery environment of the nervous system, a phospholipid bilayer barrier will spontaneously form, allowing the hydrophobic fatty acid tails from each monolayer to interact in the center of the bilayer, while being protected from the unfavorable aqueous extracellular (cerebrospinal fluid [CSF]) and intracellular milieu, which are in contact with the hydrophilic polar head groups (Figure 5–1).


Diagram of a section of a bilayer membrane formed from phospholipid molecules. The unsaturated fatty acid tails are kinked and lead to more spacing between the polar head groups and hence to more room for movement. This, in turn, results in increased membrane fluidity. (Reproduced with permission from Rodwell VW, Bender DA, Botham KM, et al: Harper’s Illustrated Biochemistry, 31st ed. New York, NY: McGraw Hill; 2018.)

A less plentiful component of the membrane is the glycolipid family, whose members contain polar head groups formed from straight or branched carbohydrate chains that extend into the extracellular medium, where they have a role in cell-to-cell recognition (Figure 5–2). Together with the much more abundant molecule cholesterol, these compounds contribute about 40% of the total lipid content of the mammalian plasma membrane. ...

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