1.68 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



resting potential, approximately the value of the po- 

 tassium potential, EsCgi, 112, 113). When the valve 

 ■ opens' the emf must suddenly change from the resting 

 value towards that of the sodium potential, £>,-,,, a 

 change to internal positivity (113). The hypothetical 

 'valve', however, is located in a physical structure, 

 the membrane, with finite resistance and capacity 

 and with both its surfaces bathed in saline media. 

 The step-like emf of the generator ' valve' must there- 

 fore distrilauie itself electrotonically o\er an area hav- 

 ing definite electrical properties, becoming a potential 

 change reduced in magnitude and distorted in form 

 (fig. 2). The simultaneous activity of a number of 

 "valves' would lead to an increased potential, thus 

 permitting gradation of the response from the mini- 

 mal observable to the full value of the electrochemical 

 potential. Since several species of ions are invoked, 

 the maximum p.s.p. strikes a i)alance ijetween the 

 different electrochemical potentials (cf. 52, 60). 



Aferlianisms of Graded Responsiveness 



The most detailed data are available on graded 

 responses of electrically excitable membrane and, al- 

 though the theory of their production is still rudi- 

 mentary, the same general process will probably be 

 found to apply also to the graded responses of synaptic 

 and sensory membrane (94-96). Graded local re- 

 sponse is usually considered to be merely a stage in 

 the events leading to the regenerative explosive activ- 

 ity which results in the spike (113). This view has 

 been invalidated by the finding (4, 6, 92) that under 

 various conditions all-or-none responsiveness can be 

 converted to a fully graded one. Only graded re- 

 sponses occur in dually-responsive insect muscle 

 fibers (37, 38) and probably in other electrically 

 excitable membranes as well (97)- The activity may 

 vary from the minimal observable to a maximal 

 response closely approximating the spike in amplitude 

 and form (fig. 18; cf. fig. 21). The degree of graded 

 responsiveness is not controlled by the membrane 

 potential as it is considered to be in current theory 



Figure 18 also illustrates how an altered local 

 excitatory state need not be caused by, nor reflected 

 in, a changed membrane potential. Whether un- 

 treated or poisoned with a drug, the single cell showed 

 subliminally enhanced excitability which w-as evi- 

 denced during an interval at least 0.2 sec. after each 

 subthreshold stimulus. The cumulative growth of this 

 "excited' state in the untreated cell led to an explosive 

 manifestation, the spike. After the cell was poisoned 



the overt manifestation look the form of a progres- 

 sively larger graded response, and this response 

 approached the spike in amplitude. 



A first approximation for revising theoretical con- 

 cepts (94, 95) con'iiders that the excitalile memiirane 

 is composed of unit areas. Each has a population of 

 electrogenic units (transducers, valves, etc.) which 

 differ amongst themselves in the threshold for their 

 excitation. In the explosively responsive population 

 the thresholds for exciting the electrogenic elements 

 of a given unit area are probably closely similar. 

 Dispersion of that population distribution could re- 

 sult in conver-^ion of all-or-none responsi\eness to the 

 graded type. 



Transfer of Activity From Postsynaptic Potentials to 

 Electrically Excitable .Membrane 



In the case of the skeletal muscle endplate or the 

 squid giant fiber synapse a relatively well-defined 

 ' patch' of electrically inexcitable synaptic membrane 

 is surrounded by electrically excitable structure. In 

 both cells, the p.s.p. is simple, only of the depolarizing 

 variety, and initiated by impulses in a single pre- 

 synaptic fiber (fig. 19). The p.s.p. then tends to be of 

 a fixed amplitude and in these two systems usually 

 causes sufficient depolarization of the contiguous 

 electrically excitable membrane to generate a spike 

 in the latter. Essentially, transmission then is one-to- 

 one, each impulse of the prefiber generating a post- 

 junctional spike. 



Under various conditions, for example upon poison- 

 ing an endplate with rf-tubocurarine, the p.s.p. de- 

 creases in amplitude and, when the depolarization 

 falls below the critical firing level, no spike is gener- 

 ated (fig. 15). The transmission block may be over- 

 come by a rapidly repetitive volley of neural stimuli 

 which successively generate new p.s.p.'s or a local 

 excitatory state before the previous ha\e disappeared. 

 The consequent augmentation of depolarizing elec- 

 trogenesis may attain the critical level and transmis- 

 sion again occurs. This general phenomenon of 

 increased effectiveness of repetitive stimuli is known 

 as facilitation. The normally occurring p.s.p. produced 

 by a given afferent neural stimulus may not be suf- 

 ficiently large to evoke a spike. Repetitive stimuli in 

 this case can summate the depolarizing p.s.p.'s and 

 facilitation is then also manifested, the summed de- 

 polarization initiating a spike. 



In the context of the electrophysiological mecha- 

 nism, a facilitated overt respon.se (e.g. of a muscle) 

 may be produced by two fundamentally different 



