SYNAPTIC AND EPHAPTIC TRANSMISSION 



'75 



evokes a brisk twitch or a maximal tetanus. The 

 slow fiber calls forth small contractions which may 

 grow slowly during repetitive stimulation. 



The apparent paradox that depolarization, an 

 electrical and unspecific stimulus, can evoke differ- 

 ent forms of response in electrically excitable mem- 

 brane has been resolved by the finding (37, 38) that 

 the membrane of the muscle fibers of the grass- 

 hopper, Romalea microptera, though electrically ex- 

 citable, responds only with graded activity. Other 

 physiological and anatomical circumstances co- 

 operate with this normally occurring graded respon- 

 siveness. The different nerve fibers evoke two degrees 

 of depolarizing p.s.p.'s in the electrically inexcitable 

 synaptic membrane. The p.s.p.'s evoked by the fast 

 nerve fiber may be larger because of greater synaptic 

 potency of the 'fast' transmitter system than in that 

 of the slow fiber (e.g. a different agent, a higher 

 concentration of transmitter, closer approximation 

 of the pre- and postsynaptic membrane or larger 

 area of synaptic contact). However, another alterna- 

 tive is that the membrane sites engaged by the 

 terminals of the different fibers are different. The 

 combination of graded p.s.p.'s and electrically 

 excitable local responses is abetted by the closeness 

 of synaptic terminations. The terminals of the fast 

 nerve fiber, spaced as close as 40/j apart, can each 

 evoke large local responses of the electrically ex- 

 citable membrane. This graded activity, summing 

 its depolarizing actions, can then evoke maximal re- 

 sponses which have the appearance of spikes. The 

 associated contraction is a twitch. The smaller 

 p.s.p.'s of the slow response can be graded in various 

 proportions and can evoke local response of various 

 degrees. The resulting contractions are also graded. 



The mechanisms involved in the dual responses 

 of muscle fibers are instructive for several reasons. 

 Dual responsiveness is probably present in muscles 

 of animals quite low in the evolutionarv scale (i 17), 

 and this suggests that electrically excitable mem- 

 brane, like the sen.sory or synaptic, was originally 

 gradedly responsivp. The ability to develop spikes 

 then would have been a later evolutionary stage (2 1 , 

 103). Dual responsiveness also represents an ex- 

 ceedingly useful mode of activity for arthropods for 

 their muscles are limited in number. The size of the 

 muscles and therefore also the numijer of their fibers 

 are limited by the exigencies of the exoskeleton. The 

 number of nerve fibers is also rather small. Despite 

 these limitations arthropods can manipulate their 

 joints intricately and with precision and carry out 

 locomotion with great dispatch and vigor. These 



different aspects of movement are all achieved with 

 an economy of means because of special responsive 

 mechanisms and anatomical conditions. 



PHARMACOLOGICAL PROPERTIES OF SYNAPSES 

 .^ND THEIR PHYSIOLOGIC.-VL CONSEQUENCES 



The discussion in this part of the present chapter 

 will be limited to vertebrate synapses, concerning 

 which information is more extensive than on in- 

 vertebrate structures. However, the pharmacology 

 of the electrically inexcitable sensory membrane of 

 the crayfish stretch receptor probably parallels that 

 of synapses in the cat brain (96). This suggests 

 that in their general aspects the pharmacological 

 properties of vertebrate and invertebrate synapses 

 will be similar in principle, although, perhaps, 

 invoKing different chemical suijstances. In crustacean 

 neuromuscular synapses and in the inhibitory 

 synapses of the stretch receptors the actions of amino 

 acid drugs parallel to a degree the effects of these 

 substances in cat brain (cf. 99, 163, and below). 

 However, other invertebrate synapses appear to 

 have no pharmacological relation to vertebrate 

 synapses (cf. 99 j. 



Classification of Drug Actions 



Depending upon the theoretical approach and the 

 experimental emphasis, several varieties of classifica- 

 tion have arisen. Thus, drugs have been grouped as 

 'mimetics' or 'lytics', graded according to the degree 

 to which they mimic or block the action of nerve 

 impulses, or sometimes of a standard comparison 

 substance (cf. 8). Particularly in describing effects of 

 drugs on the more complex synaptic systems (chiefly 

 of the central nervous system but also those of smooth 

 muscle) substances have been classified as 'excitants' 

 (or 'stimulants') and 'inhibitors' (or 'depressants'). 

 For example, since both pentylenetetrazol (Metra- 

 zol) and strychnine are convulsant agents, both 

 are classified as stimulants of the central nervous 

 system (cf. 85). Recently (cf. 156) the drugs acting 

 upon the peripheral cholinoceptive synapses of 

 skeletal muscle and autonomic ganglia have been 

 classified as 'depolarizing' or as 'nondepolarizing, 

 competitive, antagonistic inhibitors' of the latter. 

 This classification also applies to the simple depo- 

 larizing synapses of the eel electroplaques (table 2). 



An extension of this classification (table 3) has 

 proved experimentally and analytically more useful 



