Calcium-insensitive miniature endplate potentials at the neuromuscular junction.

Abstract

Several different types of acetylcholine secretion have been shown to coexist at the neuromuscular junction along with the Ca2+-dependent quantal release producing miniature endplate potentials (mepps) and endplate potentials. One of these, the Ca2+-insensitive, slow-rising mepps (slow mepps), is present in normal untreated muscles but is most prominent in many conditions where the Ca2+-dependent quantal release mechanism is not functioning properly. Slow mepps occur at a frequency of less than 0.1 Hz in normal muscles, with large variability between fibres and muscles, and can reach frequencies of 1-2 Hz in several pathological conditions. The potentials are also highly variable in size and shape, being generally of high amplitude (0.1-15 mV) and prolonged time course (1-15 ms rise time). Most importantly, slow mepps are not affected by procedures which increase the intraterminal Ca2+ concentration, including nerve stimulation, thus being unable to contribute to the function of synaptic transmission. The cellular source of the Ca2+-insensitive mepps has been determined to be the nerve terminal and not the Schwann cells or nerve sprouts. The release process producing slow mepps is generally insensitive to many drugs, ions, and procedures, stimulation being observed with vinblastine, cytochalasin B, and caffeine. Depression of this secretion is effected by uncouplers of oxidative phosphorylation and by a drug (AH5183) which inhibits the vesicular active acetylcholine transport system. It is concluded that the slow mepps are due to an exocytic fusion of unique synaptic vesicles with the plasma membrane near the active zones, in a process insensitive to many intracellular ions and regulators. Since slow mepps are prominent in many pathological conditions of nerve and muscle, it is speculated that they play some role in the recovery or development of synaptic function.