INITIATION OF IMPULSES AT RECEPTORS 



'39 



this theoretical displacement from that observed 

 (fig. lo left) leaves a 'dynamic component' (fig. 

 10 right); it can be seen that this component is 

 transmitted with less attenuation to the center of the 

 end organ, and also that its time course is similar to 

 that of a receptor potential (fig. 4C). It seems there- 

 fore that the rapid adaptation of this receptor is 

 primarily a mechanical phenomenon. Since neither a 

 change in axon length nor a bending of the axon has 

 been detected, it seems that radial displacements of 

 the axon itself, or of the tissues immediately sur- 

 rounding it, are responsible for activating the re- 

 ceptor. 



EFFECTS OF TR.'SiNSMITTER SUBSTANCES 



A number of investigations into the actions of 

 acetylcholine, epinephrine, histamine and related 

 compounds have been carried out. These investiga- 

 tions have in general had one of two objecti\es: one, 

 to see if these substances are normally involved in the 

 initiation of impulses by receptors; the other, to see 

 if there is specialization of the membrane of the ter- 

 minal part of the sensory axon. 



Action of Acetylcholine 



Acetylcholine has been shown to increase or initiate 

 a discharge of impulses from a variety of sensory 

 receptors. These include mechanical receptors from 

 the skin of the cat and the dog (13, 23), from the cat's 

 carotid sinus (17, 64), from the crayfish stretch re- 

 ceptor (102), the cat's tongue (62) and from the 

 frog's skin (53); also thermal receptors in the cat's 

 tongue (21) and chemical receptors of the cat's 

 tongue (62) and carotid body (98). Succinylcholine 

 has been found to increase the activity of mammalian 

 muscle spindles (33). Finally acetylcholine has been 

 found to effect and even initiate sensations in the 

 human subject; these include pain (7, 44, 90) and 

 thermal (10) sensations. Many of these investigations 

 include control experiments designed to show that 

 these are direct effects on the sensory pathway and 

 are not secondary to contractions of smooth or striated 

 muscle and do not result from excitation of the auto- 

 nomic nervous system. It seems clear therefore that 

 acetylcholine does have an action on some part of the 

 sensory pathway, and since similar applications of 

 acetylcholine to nerve fibers (53, 70) or to pregangli- 

 onic nerve terminals (11, 14) are ineffective, it seems 

 likely that these results represent a direct action of 



the substance on the receptor mechanism itself. The 

 dosage and pharmacological pattern of these re- 

 sponses vary from one preparation to another. The 

 most common picture is that represented by the ex- 

 periments on the mechanical receptors of cats and 

 frogs in which responses were recorded directly from 

 the primary sensory nerve fibers. These responses are 

 produced by doses of the same order of magnitude as 

 those required to excite the skeletal neuromuscular 

 junction. They are unaffected by atropine, but are 

 blocked by curare or excess nicotine; smaller doses 

 of nicotine beha\e like acetylcholine. The picture is 

 thus very similar to that of the acetylcholine action at 

 synapses and the skeletal neuromuscular junction. 

 The main divergence from this pattern is that atropine 

 blocks the acetylcholine effect in the crayfish stretch 

 receptor (102). Atropine has also been found to raise 

 the thresholds for the sensations of pain (90) and of 

 cold (lo) in the human; its mode of action in these 

 instances is not at present clear. 



There has Ijeen some difference of opinion as to 

 whether acetylcholine can act independently or 

 whether it merely sensitizes the receptor to the 

 natural stimulus; it is possible that the action may be 

 different in different preparations. In some prepara- 

 tions, as shown in figure 12, there is no doubt that 

 acetylcholine can initiate a discharge (17) and that 

 the action of acetylcholine summates with the physio- 

 logical stimulus (17, 53). In the frog's skin acetyl- 

 choline does not effect the time course of excitation 

 or recovery but does lower the threshold and increase 

 the rate of adaptation (53). The most likely explana- 

 tion of the action of this substance is that it depolarizes 

 the membrane of the terminal portions of the sensory 

 nerve fiber and that this action is confined to those 

 parts that take part in the generation of the receptor 

 potential. This conclusion might lead one to suppose 

 that acetylcholine plays some part in the normal re- 

 sponse to a physiological stimulus. This, however, 

 seems very doul)tful in the light of results obtained 

 with blocking agents and anticholinesterases. 



Action oj Blocking Agents and Anticholinesterases 



It has been stated above that the action of acetyl- 

 choline on sensory receptors is blocked by curare. It 

 is also blocked by hexamethonium (17, 23), and large 

 doses of nicotine (13). While these substances block 

 the action of a subsequent dose of acetylcholine or 

 nicotine, they have no effect, in most preparations, on 

 the normal response to a physiological stimulus. Thus 

 the mechanical receptors of the carotid sinus of the 



