ABSTRACT
In 1950 Fatt and Katz reported the existence of ‘biological noise’ when recording the endplate potential (epps) at the amphibian neuromuscular junction with an intracellular microelectrode. Subsequently they gave a full account of these ‘miniature potentials’, showing that they had many of the physiological characteristics of the epp, and that the amplitudes of these miniature end-plate potentials (mepps) followed a Gaussian distribution (Fig. 1A; Fatt and Katz, 1952a). They also noted that ‘lack of calcium apparently reduces the epp in definite “quanta”, as though it blocks individual nerve terminals, or active patches within them, in an all-or-none manner’ and that under these conditions ‘the normal epp can be seen…, to break down into individual miniature units’. Thus the epp was seen as composed of mepps. This gave rise to the ‘quantal hypothesis’ namely that the mepp represented a quantum of transmitter release and the epp multiples of this quantum. Furthermore, ‘suppose…that there are within the terminal area some 100 discrete “patches” concerned with the release of ACh. If these terminal structures have a special tendency to spontaneous excitation, then our observations would be easily understood”. So the concept of discrete zones for the secretion of transmitter had a physiological basis. These ideas were to be given substantial impetus with introduction of the electron microscope for the examination of end-plate structure. This revealed synaptic vesicles in the nerve terminal, giving rise to the ‘vesicle hypothesis’ that the miniature units or quanta are due to the prepackaging of transmitter in vesicles (Birks et al., 1960). Furthermore, the ultrastructural observations of these authors that ‘one often sees the vesicles concentrated in certain well-defined areas focussed on a dense zone of the axon membrane directly opposite a post-synaptic fold’ which they referred to as ‘special zones of the axon membrane’ introduced the idea that such zones were the ‘discrete zones’ from which quanta are released. This gave rise to the ‘active zone hypothesis’, namely that these zones constitute the sites of quantal transmitter release.
