The Number of Acetylcholine Molecules in a Quantum and the Interaction between Quanta at the Subsynaptic Membrane of the Skeletal Neuromuscular Synapse

A common feature in the design of both excitatory and inhibitory chemical synapses is the release of transmitter in multimolecular packets or quanta (for references, see Katz 1969). Electrophysiological studies of the quantal nature of synaptic transmission, particularly by Katz and his colleagues, have been performed most extensively on the skeletal neuromus-cular synapse. There, acetylcholine (ACh) is the ex-citatory transmitter, which, upon release, diffuses across the synaptic left and combines with receptors in the postsynaptic membrane. This leads to a transient con-ductance change that produces a depolarization of the muscle. In the context of this scheme, we shall focus on the ACh quantum and consider three specific questions. First, how many ACh molecules are there in a quan-tum? Second, does the ACh released in a quantum activate all of the available receptors? And third, do the ACh molecules released from neighboring quanta affect overlapping postsynaptic areas, and if so, do they influence each other's action? This paper summarizes results, recently reported elsewhere in detail (Hartzell et al. 1975; Kuffler and Yoshikami 1975a,b), showing that (1) there are fewer than 10,000 molecules of ACh in a quantum; (2) the ACh in a quantum does not saturate the postsynaptic receptors; (3) quanta normally act independently of each other on the postsynaptic membrane; and (4) with acetylcholine sterase inhibited, ACh is free to diffuse within the synaptic left, leading to a potentiat-ing interaction between quanta