In addition to ATP-powered ion pumps, which transport ions against their concentration gradients, the plasma membrane contains channel proteins that allow the principal cellular ions (Na⁺, K⁺, Ca²⁺, and Cl⁻) to move through them at different rates down their concentration gradients. Ion concentration gradients generated by pumps and selective movements of ions through channels constitute the principal mechanism by which a difference in voltage, or electric potential, is generated across the plasma membrane. In other words, ATP-powered ion pumps generate differences in ion concentrations across the plasma membrane, and ion channels use these concentration gradients to generate a tightly controlled electric potential across the membrane (see Figure 11-3).

In all cells, the magnitude of this electric potential is generally ~70 millivolts (mV), with the inside cytosolic face of the plasma membrane always negative with respect to the outside exoplasmic face. This value does not seem like much until we consider that the thickness of the plasma membrane is only ~3.5 nm. Thus the voltage gradient across the plasma membrane is 0.07 V per 3.5 × 10⁻⁷ cm, or 200,000 volts per centimeter! (To appreciate what this means, consider that high-voltage transmission lines for electricity use gradients of about 200,000 volts per kilometer, 10⁵-fold less!)

The ionic gradients and electric potential across the plasma membrane play crucial roles in many biological processes. As noted previously, a rise in the cytosolic Ca²⁺ concentration is an important regulatory signal, initiating contraction in muscle cells and triggering in many cells secretion of proteins, such as digestive enzymes from pancreatic cells. In many animal cells, the combined force of the Na⁺ concentration gradient and the membrane electric potential drives the uptake of amino acids and other molecules against their concentration gradients by symporters and antiporters (see Figure 11-3 and Section 11.5). Furthermore, electrical signaling by neurons depends on the opening and closing of ion channels in response to changes in the membrane electric potential (see Chapter 22).

Here we discuss the origin of the membrane electric potential in resting non-neuronal cells (often called the cell’s resting membrane potential); how ion channels mediate the selective movement of ions across a membrane; and useful experimental techniques for characterizing the functional properties of channel proteins.