Action potentials are discrete electrical signals that are transmitted along the length of axons and propagate information within the nervous system. These signals are generated as a result of a transient change in membrane permeability: from a state where it is more permeable to potassium (K+) than sodium (Na+), to a reversal of these permeability properties. During the action potential, an influx of Na+ is responsible for rapid depolarization and an efflux of K+ causes repolarization or hyperpolarization. These changes in membrane permeability are due to the opening and closing of voltage-gated ion channels. The speed at which action potentials are conducted is based on the radius of the axon, the presence of a myelin sheath, and the number of ion channels.
When the neuron is at rest, there is an excess of positive charge on the outside of the cell (positive potential) and an excess of negative charge on the inside of the cell (negative potential). This creates the resting membrane potential, which is measured by recording the voltage inside the cell relative to the outside in the extracellular fluid. For most neuron types, resting membrane potential is usually −70 mV; however, it may be between −40 and −90 mV depending on the brain region. An electrical potential difference exists across the plasma membrane of cells and is created by differences in the concentration of charged ions between the cytosol and interstitial fluid. The equilibrium potential, the electrical potential generated across the membrane, can be predicted with the Nernst equation. The two major ions involved in maintaining a resting potential and generating an action potential are K+ and Na+.
At rest, Na+ ions slowly leak into the cell as a result of two forces: a Na+ concentration gradient and the electrostatic force of anions inside the cell. The membrane is relatively permeable to K+ ions that have the tendency to move down their concentration gradient: from the inside to the outside of the cell. Two negatively charged anions are also important to establish the membrane potential: chloride (Cl−) and organic anions.
An ionic pump, the Na+ and K+ ATPase (or Na+/K+ pump), is a membrane-bound protein that maintains the concentration gradient for Na+ and K+. This pump creates a natural imbalance in the concentration of K+ and Na+ on either side of the plasma membrane. Adenosine triphosphate (ATP) provides the energy to actively pump three Na+ ions out of the cell while two K+ ions are pumped into the cell. This results in an intracellular concentration of K+ that is 20 times higher than the extracellular concentration of K+. The concentration gradient of Na+ runs in the opposite direction, with a concentration that is 10 times higher outside the cell compared to the Na+ concentration inside the cell. Overall, this results in a net increase in positive charges on the outside of the cell.
Voltage-gated sodium channels (VGSC) embedded within the phospholipid membrane play an important role in the generation of an action potential. The VGSC is selectively permeable to Na+ ions but is normally closed. Na+ ions have a great desire to be inside the cell as a result of two electrochemical forces: Na+ wants to equilibrate its concentration between the outside and inside of the cell, and it wants to neutralize the charge difference between the inside and outside of the cell. Depolarization of the membrane stimulates the opening of VGSC, allowing Na+ to rush into the cell. The initial depolarizing event must change the membrane potential by about 15—30 mV for the event to occur. This is known as the threshold of excitation.
At peak depolarization, Na+ channels close and voltage-dependent ion channels that are only permeable to K+ open. The opening of these channels increases potassium permeability, allowing K+ ions to rapidly travel outside the cell down its concentration gradient. This is known as repolarization. As K+ continues to travel outside of the cell, the membrane becomes slightly hyperpolarized or more negative. While the membrane is hyperpolarized, another action potential cannot be generated. Following the completion of an action potential, all ion channels return to their resting state and the activity of the Na+/K+ pump returns the membrane potential to its normal resting state.
Action potentials are self-propagating, meaning that depolarization of a small region of the membrane triggers the opening of nearby Na+ channels. In this way, a wave of depolarization travels along the nerve. Once an action potential is triggered in one region of the membrane, the voltage Na+ channels become temporarily inactivated, preventing it from doubling back. This is referred to as the refractory state. Action potentials are referred to as “all-or-none” events, meaning that all action potentials are identical when it comes to the magnitude of the membrane depolarization. In contrast, the initial membrane depolarization is a graded response.
See also: Axon; Membrane Potential: Depolarization and Hyperpolarization; Nerves
Fletcher, Allan. (2011). Action potential: Generation and propagation. Anaesthesia & Intensive Care Medicine, 12(6), 258—262.
Fry, Chris H., & Rita I. Jabr. (2010). The action potential and nervous conduction. Surgery (Oxford), 28(2), 49—54.