Quantal or Graded Secretion of Adrenal Medullary Hormone and Sympathetic Neurotransmitter

Abstract

One and a half decades have gone by since the concept of quantal secretion of neurotransmitter was originally introduced (for refs. see Katz, 1969). The initial work was done on the skeletal neuromuscular endplate, but it appears that the postjunctional membrane potential (MP) in essentially all neuro-effector junctions so far investigated shows extensive similarities to that of the endplate. Thus in the absence of nerve impulses there are spontaneous subthreshold spike-like fluctuations in the MP, similar to the MEPP (miniature endplate potentials) of the neuromuscular endplate, and on nerve stimulation the MP does not rise continuously but in steps, to a level above the resting potential in some instances apparently corresponding to an integral number of the amplitude of a single MEPP. Since focal application of exogenous acetylcholine to the neuromuscular endplate does not produce a stepwise, but a smoothly graded rise in MP, the important conclusion has been drawn that the chemoreceptors of the postjunctional membrane are not enough sensitive to detect, or to signal the detection of, single transmitter molecules. It has thus been postulated that the spontaneous miniature potentials are not due to diffuse leakage of transmitter, but to the impact on the postjunctional membrane of focally secreted multimolecular packets of transmitter, of preset size. The electronmicroscopical findings of vesicular structures accumulating in nerve terminals, and the subsequent demonstration by biochemical techniques that these “synaptic vesicles” are loaded with neurotransmitter, led to the assumption that the transmitter quanta are stored in and secreted from the vesicles, or “transmitter granules”, and that the size of the quantum is possibly determined by their total content of transmitter.