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HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY 1 



common (179) and the electrically inexcitable secre- 

 tory cells of the adrenal medulla are regarded as 

 second order autonomic neurons (cf. i 77). 



The conductile portion of the neuron, generating 

 all-or-none spikes and therefore capable of decre- 

 mentless propagation, requires electrical excitability 

 for this function. It is probably a later evolutionary 

 development (21) brought about in the course of 

 extension of the cells in the metazoa and of their 

 participation in complexly organized activity. That 

 the conductile activity represents a new evolutionary 

 step, mediated by a structure interposed between the 

 primitive input and output sections, is also suggested 

 by the absence of conductile electrogenesis in gland 

 cells and by their electrical inexcitability (96, 97). 

 The occurrence of muscle fibers which are also not 

 electrically excitable and which generate no spikes 

 (4, 34, 35, 97) reinforces this view. Classifying distinc- 

 tions with respect to excitability and the types of 

 responses of electrogenic membranes are by no means 

 exhaustive of the different varieties. Pharmacological 

 differences of various kinds specify an even greater 

 diversity amongst excitable, electrogenic membranes. 

 These differences are not to be seen by anatomical 

 methods, nor indeed, by electrophysiological means 

 alone, since pharmacologically distinct varieties of 

 membrane can all generate similar types of electrical 

 responses (fig. 14III). 



Transmitter Actions 



The varieties of transmitters will be treated below; 

 the present discussion will be confined to the general 

 electrophysiological aspects. From this point of view, 

 the precise chemical natures of the substances are of 

 little moment, the important feature being that they 

 all activate synaptic electrogenesis. It is unlikely that 

 the sign of the p.s.p. is affected by the excitant agent. 

 Thus, as noted above, acetylcholine is a 'depolarizing' 

 substance for excitatory p.s.p.'s but activating inhibi- 

 tory synapses, as in the pacemaker of the heart it is a 

 " hyperpolarizing' agent. The characteristics of the 

 transmitters will, however, determine to .some extent 

 the character of the p.s.p. a) For example, if the 

 transmitter is a large complex molecule, it is unlikely 

 that it would be available in large concentrations at 

 the terminals of the presynaptic element. The amount 

 of total excitant might therefore be limited in propor- 

 tion to the quantity secreted during a single activity. 

 Thus, a single afferent volley might cause a number 

 of p.s.p.'s, but repetitive activity might rapidly ex- 

 haust the available transmitter, b) Molecular dimen- 



sions and configurations might also determine the 

 rapidity of diffusion of the transmitter from its site of 

 release to its site of action. The distances involved, 



o 



although probably only about 100 A are significant 

 in terms of molecules, c) The kinetics of interaction 

 between the transmitter and the postsynaptic electro- 

 genic surface may also be in part determined by the 

 transmitter itself. For example, it is conceivable that 

 two different agents might act on similar synaptic 

 sites with different kinetics, giving rise to differences 

 in the p.s.p.'s evoked by each. Studies in kinetics of 

 these interactions are only now beginning (cf 53, 127) 

 and the nature of interaction is as yet unknown. 

 Analogy with other processes is usually invoked and 

 two models which are at present fashionable, actisa- 

 tion processes of enzyme reactions and antigen- 

 antibody combinations, are not necessarily mutually 

 exclusive. The transmitter agent is presumed to com- 

 bine with some ' receptor' sites of the synaptic mem- 

 brane (cf 2, 9, 14). (f) The chemical properties of the 

 transmitter may also determine the characteristics of 

 the p.s.p. Thus, a labile agent such as acetylcholine 

 may be rapidly destroyed, and it might give rise to 

 shorter p.s.p.'s than would a more stable excitant of 

 the same synaptic site (cf. 53). Likewi.se, the degree 

 of chemical binding between the transmitter and the 

 ' receptor' or the stability of the complex may play 

 similar roles in determining the duration of the p.s.p., 

 or in its 'competitive' behavior toward an inactivating 

 synaptic drug. /) Although a transmitter agent may 

 activate a given type of receptor it may also be an 

 inactivator of other types. Thus, the transmitter at 

 inhibitory synapses of some invertebrate muscle fibers 

 is thought to be an inactivator of the excitatory syn- 

 apses (68, 73). g~) A given synaptic complex might be 

 composed of several \arieties of receptors, although 

 all generating the same kind of p.s.p. Yet, one trans- 

 mitter might inactivate some of the receptors while 

 another transmitter did not, and the p.s.p.'s would 

 vary accordingly. 



Two of the factors, the transit time of the trans- 

 mitter across the synaptic gap (6 in the preceding) 

 and an induction period (c above), probably deter- 

 mine the synaptic latency as noted earlier. Together 

 these two processes may last several milliseconds. 



Genesis nf Postsynaptic Potentials 



Important information on this matter derives from 

 the occurrence of spontaneous 'miniature' p.s.p.'s at 

 muscle endplates. Probably this activity is generated 

 bv random releases of transmitter from presynaptic 



