The Resting Membrane Potential Is the Result of Three Major Determinants

Three major factors cause the resting membrane potential.

1. The Na⁴_fIC pump. Cell membranes have an energy­dependent pump that pumps Na^τ ions out of the cell and draws K* ions into the cell against their concentration gradients.

2. An ion species will move toward a dynamic equilibrium if it can flow across the membrane. Using K⁺ as an example, the concentration difference across the membrane actively maintained by the Na⁴,K⁴ pump produces a concentration gradient, or “chemical driving force,” that attempts to push the ion passively across the membrane from high concentration inside the cell toward low concentration outside. If K’ can flow across ion channels in the membrane, exiting K⁴ leaves behind unopposed negative charge (often from negatively charged protein macromolecules trapped inside the cell) that builds an electrical gradient, or “electrical driving force,” pulling K* back inside the cell. These opposing gradients eventually produce a dynamic equilibrium, even though there may still be more K‘ inside than outside, as well as a charge imbalance across the membrane. This uneven distribution of charge at dynamic equilibrium produces a voltage across the membrane called the equilibrium potential for that ion. When an ion species can flow across a channel in the membrane, it flows toward its equilibrium state, and it drives the voltage across the membrane toward its equilibrium potential.

3. Differential permeability of the membrane to diffusion of ions. The resting membrane is much more permeable to K¹ than to Na⁺ ions because there are vastly more K⁺ leak channels than Na⁴ leak channels in the membrane. This greater membrane permeability to K* means that K⁺ ions can more closely approach their dynamic equilibrium state, and equilibrium potential, compared with Na* ions, which have difficulty moving across the membrane. Therefore the equi­librium potential for the more permeant K⁴ ions (about -90 mV in many mammalian neurons) will have the pre­dominant influence on the value of the resting membrane potential compared with the equilibrium potential of the vastly less permeant Na' ions (about +70 mV in many mammalian neurons). Therefore, as noted earlier, the resting membrane potential of many mammalian neurons is about -70 mV, close to the equilibrium potential for K⁴.

These three determinants—the Na⁴,K⁴ pump, the movement of a permeant ion toward dynamic equilibrium, and the differentially permeable membrane—are the primary source of the resting membrane potential. The value of this potential can be predicted by the Nernst and Goldman equa­tions, and the reader is referred to Chapter 1 and to the bibli­ography for a more quantitative understanding of the resting membrane potential.

This discussion of the resting membrane potential has a number of important clinical implications. The Na⁴,K⁴ pump requires energy in the form of adenosine triphosphate (ATP), which is derived from the intracellular metabolism of glucose and oxygen. In fact, it has been estimated that 50% to 70% of the brains ATP-derived energy is expended on the pump. Because the neuron cannot store either glucose or oxygen, anything that deprives the nervous system of either substrate can lead to impairment of the pump and serious clinical neurological deficits. Fortunately, hormones and other factors normally maintain serum glucose and oxygen levels within narrow limits. Because Na' and K⁴ are important ions involved in establishing the resting membrane potential, it is essential that serum levels of Na* and K⁴ be regulated carefully. The endocrine system (Chapter 33) and kidney (Chapter 41) main­tain serum Na’ and K* levels within narrow limits. Anything altering serum levels of either ion beyond normal limits also leads to potentially severe neurological deficits.