Anatomy and Physiology

Polarization is established by maintaining an excess of sodium ions (Na ⁺) on the outside and an excess of potassium ions (K ⁺) on the inside. A certain amount of Na ⁺ and K ⁺ is always leaking across the membrane through leakage channels, but Na ⁺/K ⁺ pumps in the membrane actively restore the ions to the appropriate side.

The main contribution to the resting membrane potential (a polarized nerve) is the difference in permeability of the resting membrane to potassium ions versus sodium ions. The resting membrane is much more permeable to potassium ions than to sodium ions resulting in slightly more net potassium ion diffusion (from the inside of the neuron to the outside) than sodium ion diffusion (from the outside of the neuron to the inside) causing the slight difference in polarity right along the membrane of the axon.

Other ions, such as large, negatively charged proteins and nucleic acids, reside within the cell. It is these large, negatively charged ions that contribute to the overall negative charge on the inside of the cell membrane as compared to the outside.

In addition to crossing the membrane through leakage channels, ions may cross through gated channels. Gated channels open in response to neurotransmitters, changes in membrane potential, or other stimuli.

The following events characterize the transmission of a nerve impulse (see Figure 1):

• Resting potential. The resting potential describes the unstimulated, polarized state of a neuron (at about –70 millivolts).
  
• Graded potential. A graded potential is a change in the resting potential of the plasma membrane in the response to a stimulus. A graded potential occurs when the stimulus causes Na ⁺ or K ⁺ gated channels to open. If Na ⁺ channels open, positive sodium ions enter, and the membrane depolarizes (becomes more positive). If the stimulus opens K ⁺ channels, then positive potassium ions exit across the membrane and the membranehyperpolarizes (becomes more negative). A graded potential is a local event that does not travel far from its origin. Graded potentials occur in cell bodies and dendrites. Light, heat, mechanical pressure, and chemicals, such as neurotransmitters, are examples of stimuli that may generate a graded potential (depending upon the neuron).

The following four steps describe the initiation of an impulse to the “resetting” of a neuron to prepare for a second stimulation:

1. Action potential. Unlike a graded potential, an action potential is capable of traveling long distances. If a depolarizing graded potential is sufficiently large, Na ⁺ channels in the trigger zone open. In response, Na ⁺ on the outside of the membrane becomes depolarized (as in a graded potential). If the stimulus is strong enough—that is, if it is above a certain threshold level—additional Na ⁺ gates open, increasing the flow of Na ⁺ even more, causing an action potential, or complete depolarization (from –70 to about +30 millivolts). This in turn stimulates neighboring Na ⁺ gates, farther down the axon, to open. In this manner, the action potential travels down the length of the axon as opened Na ⁺ gates stimulate neighboring Na ⁺ gates to open. The action potential is an all‐or‐nothing event: When the stimulus fails to produce depolarization that exceeds the threshold value, no action potential results, but when threshold potential is exceeded, complete depolarization occurs.
2. Repolarization. In response to the inflow of Na ⁺, K ⁺ channels open, this time allowing K ⁺ on the inside to rush out of the cell. The movement of K ⁺ out of the cell causes repolarization by restoring the original membrane polarization. Unlike the resting potential, however, in repolarization the K ⁺ are on the outside and the Na ⁺ are on the inside. Soon after the K ⁺ gates open, the Na ⁺ gates close.
3. Hyperpolarization. By the time the K ⁺ channels close, more K ⁺ have moved out of the cell than is actually necessary to establish the original polarized potential. Thus, the membrane becomes hyperpolarized (about –80 millivolts).
4. Refractory period. With the passage of the action potential, the cell membrane is in an unusual state of affairs. The membrane is polarized, but the Na ⁺ and K ⁺ are on the wrong sides of the membrane. During this refractory period, the axon will not respond to a new stimulus. To reestablish the original distribution of these ions, the Na ⁺ and K ⁺ are returned to their resting potential location by Na ⁺/K ⁺ pumps in the cell membrane. Once these ions are completely returned to their resting potential location, the neuron is ready for another stimulus.