What are extrajunctional receptors?
The ability of cells to make receptors is genetically encoded. The nicotinic receptor of the neuromuscular junction is made up of five proteins inserted into the cell membrane. Two of these five proteins are identical (referred to as α proteins). The extracellular projections of these two (of the five transmembrane proteins that form the receptor) are the binding sites for acetylcholine. Receptors, like most cellular proteins, turn over. The acetylcholine receptors turn over with half-lives of 1–10 days. They are inserted almost exclusively at the motor endplate near a nerve terminal. It is felt that the active nerve terminal must have some influence on recep-tor location, though the mechanism has not yet been determined. On removal of this neural influence, receptor density increases at the endplate and receptors begin appearing beyond the endplate.
These extrajunctional receptors occasionally have a minor structural difference from the normal acetylcholine receptor. One of the five protein chains may have a single different amino acid substitution. This structural differ-ence can lead to a functional difference. When activated (e.g., by succinylcholine) they allow a greater exchange of ions across the cell membrane than the normal receptor. The ability to produce altered receptors also seems to be genetically encoded. Altered receptors are found in fetal tissue before neurologic development reaches a stage where it can influence muscle cells to insert adult nicotinic recep-tors at the neuromuscular junction.
Extrajunctional receptors are of significant clinical con-sequence. Interaction of succinylcholine with extrajunc-tional receptors results in massive efflux of potassium (K+) from the cell, resulting in an acute rise in serum K+.