6o 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



Studies (21, 22, 2;5, 48, 66, 67, 70) have revealed it as a 

 boundary membrane of uniform thickness, about 

 50 A, which stands out with remarkable clarity from 

 the interior of the neuron and its surround. There is 

 much more uncertainty with respect to the chemical 

 composition of the membrane, which generally is sup- 

 posed to be a thin, proi)ai)ly bimolccular, layer of 

 mixed phospholipids and cholesterol, supported by a 

 protein framework. It is further postulated that the 

 transport of molecules and ions across this membrane 

 is largely a diffusion process, the respective net move- 

 ments being determined by the electrochemical 

 potentials However, metabolic energy must also be 

 made available for net transport against the electro- 

 chemical gradients of such ions as sodium and potas- 

 sium. With some memljranes, it is also necessary to 

 postulate that specific permeability functions are 

 'built in'; for example, in all membranes giving the 

 self-regenerative responses that are characteristic of 

 impulses, depolarization initiates a brief permeability 

 to sodium ions; and at excitatory synapses the excita- 

 tory transmitter substance probably causes the mem- 

 brane to become like a sieve with pores permeable to 

 all small ions, while at inhibitory synapses the inhib- 

 itory substance causes much more selective ion 

 permeability, which may, however, be due to a still 

 finer sieve-like structure. 



It will emerge in the sub.sequent .sections on neuron 

 physiology that as yet very little functional significance 

 can be attached to all the detailed structural features 

 occurring within neurons, which are well described in 

 a recent review by Young (79). At the present level of 

 understanding, the behavior of neurons is explained in 

 terms of the properties of their surface membranes, 

 including the specialized surface membranes of the 

 synaptic regions. The interior is assigned a function 

 merely on account of its ionic composition and its 

 specific conductance. Doubtless this unsatisfactory 

 state of affairs will be remedied as new insights are 

 gained into the metabolic functions of the nerve cell 

 and their integration with the membrane functions. 



Some beginnings have already been made. For 

 example, energy derived from metabolic processes in 

 the neuron is necessary in order to move ions across 

 the surface membrane against their electrochemical 

 potentials. There is now evidence that, with the 

 linked transfer of sodium outwards and potassium 

 inwards, the rate of this ionic pump is determined by 

 the internal concentration of sodium ions (15, 16, 53, 

 54). Another correlation between the neuron interior 

 and the surface membrane is beginning to emerge in 

 relation to the synaptic vesicles in the presynaptic 



terminals. There is evidence .supporting the postulate- 

 that these vesicles are concerned in the quantal 

 emission of transmitter from the presynaptic terminals- 

 of the neuromuscular junction (26, 63, 70); and that 

 the level of the membrane potential of the presynaptic 

 terminals determines the rate of emission of quanta 

 therefrom, the rate rising by more than a million-fold 

 during a nerve impulse. Thus it has been postulated 

 that in some way the properties of the .surface mem- 

 brane are able to influence profoundly the state of 

 relatively large structures (spheres of 300 to 500 A in 

 diameter) in the immediately adjacent cytoplasm 

 (26, 63); and, by analogy, a similar postulate has been 

 suggested for the synaptic vesicles which also form 

 characteristic features of all synaptic junctions that on 

 other grounds are regarded as functioning by chemical 

 transmission (21, 29, 67). 



The internal structure of neurons is profoundly 

 altered in pathological states induced, for example, by 

 section of the axon or by the action of toxins (4). 

 There is good evidence that such a striking feature as- 

 the Nissl substance or ergastoplasm is concerned in 

 the protein manufacture that occurs during growth 

 and regeneration (58). But as yet there is little under- 

 standing of the ' trophic' action which the cell body 

 exercises on the axon, apparently by maintaining an 

 intra-axonic pressure and a continual tran.sfcr of 

 material along the fiber (79). 



Electronmicroscopy has already contributed much 

 information that is of the greatest value in interpreting 

 the mode of operation of synapses. Despite the very 

 wide range in the grosser features of synapses, at the 

 electronmicroscopic level there is a remarkable simi- 

 larity between all synapses that are believed to work 

 by a chemical transmitter mechanism (fig. i). Es.sen- 

 tially, in these structures considerable areas of the 

 presynaptic and postsynaptic membranes are sepa- 

 rated bv a very narrow cleft that shows a remarkable 

 uniformity in width for any one type of synap.se and 

 that varies in width from 150 to 500 A with different 

 types Presumably, this accurate apposition of the 

 two membranes is maintained by some structural 

 linkage across the cleft, which appears in elcctron- 

 microphotographs as a granular material The pre- 

 synaptic and postsynaptic membranes are continuous 

 with the surface membranes of their respecti\e cells, 

 neurons or effector cells, and as yet ha\e not been 

 shown to have any distinctive structural features 

 except the deep transverse folds that distinguish the 

 subsynaptic mu.scle membrane at the neuromuscular 

 junction (figs. iZ), E) (19, 69, 70). Finally, in all 

 cheinical-transmitting synapses the presynaptic termi- 



