126 PHYSIOLOGICAL TRIGGERS 



brane 'carrier' molecules of unknown nature (cf. 113). However, it would also 

 seem possible to construct a model based on membrane pores, electrostatically 

 controlled in size by alteration of their molecular walls (cf. 149). The relative 

 depth of the pores with respect to the ionic diameters would facilitate selective 

 movement of Na+ inward (114, 173). 



b) Graded Response. It is not likely that the three processes postulated in 

 the Hodgkin-Huxley theory exhaust the number of membrane molecular 

 events of excitation and electrogenesis. For example (103), depolarization of a 

 1.2-centimeter region of a squid giant axon by increasing external K+ rapidly 

 causes loss of responsiveness in this region, which is ascribable to the depolari- 

 zation of the axon and consequent sodium inactivation. However, after re- 

 moving the excess K+, recovery of responsiveness and of propagation develops 

 rapidly while the membrane is still depolarized and, therefore, presumably 

 sodium conductance is still inactivated.^ 



The occurrence of graded responsiveness to electrical stimuli also indicates 

 that additional membrane events are involved in electrogenic activity. When 

 treated with one of a variety of compounds (J-tubocurarine, DFP, eserine, 

 procaine, tertiary prostigmine) the eel electroplaque loses all-or-nothing re- 

 sponsiveness (6). The activity is then graded with the strength of the electrical 

 stimulus, and becomes decrementally propagated, but the maximal response 

 resembles the normal spike in form and amplitude. This change must be 

 ascribed to some alterations of membrane constituents by drug action, since 

 the resting potential is not affected and the potential-determined 'sodium in- 

 activation' could, therefore, not play a role. 



Graded responsiveness, involving large but localized spike-like activity, and 

 sudden transition to all-or-nothing propagated responses, has also been found 

 during the refractory period of eel electroplaque (fig. 2) and squid, earthworm 

 and crayfish giant axons (7, 98, 102, 122-125), and in dog cardiac muscle (115). 

 Some invertebrate muscle fibers react to electrical stimuli only with graded 

 response (85, 107). Lloyd (140) has described a presynaptic potential in dorsal 

 root afferent terminals, which is similar to the post-synaptic potential of 

 motoneurons (20), and differs radically from the spike of the afferent axon. 

 This response might be graded^: 



These findings seem to indicate, therefore, that graded responsiveness to 

 electrical stimuli is a general property upon which in certain excitable tissues 



* The ability of some vertebrate nerve fibers (142) and invertet)rate muscle fibers (73) to 

 remain electrogenic, although with a radically altered response, when external Na+ is sub- 

 stituted by certain organic ions, is still an unexplained phenomenon. 



* Loss of proj^agative activity, but persistence of local and therefore ])resuniably graded 

 responsiveness, has been noted in various tissues. Eccles and O'Connor (65) found that at some 

 levels of curarization the neurally excited frog muscle is capable of local 'abortive spikes.' 

 Vertebrate axons are electricallj' responsive, but do not propagate during the 'functional 

 refractory period' (170). Procaine poisoned muscle is still capable of excitation localized to 

 the cathodal stimulating region (175). An interesting, but as \'et inadequately studied phe- 



