1028 



11 WllHili IK HI I'HV Slul i HA 



\i i ri ipiiysk )i.oc;v 111 



aerates for lack of enzymes reaching it from the 

 cell body [see Gerard (83)] has been supported by 

 extensive evidence (296) that there is indeed a steady 

 movement of particular substances (258), even of 

 synaptic vesicles (282), if not of the entire proto- 

 plasm, peripherally alone; each nerve fiber (29,1). 

 This rate of movement is similar to the actual rate of 

 regeneration and demands, for the long fibers, a daily 

 synthesis by the perikaryon of new protoplasm equal 

 to three times iis own volume. Such rapid turnover 

 also relates to the character of the cell nucleus, the 

 rapid changes in Xissl substance and other nuclein 

 material, the high energy requirements, and the 

 movement of transmitter and other neurohumoral 

 substances along a nerve fiber. Neurons and nerve 

 fibers continue to function quite well after several 

 hours soaking in ribonuclease [RXA is gone on fixa- 

 tion, but the time of enzyme penetration is not es- 

 tablished, according to Maynard (personal com- 

 munication)] or after exposure to proteolytic enzymes 

 (280); yet certain nucleotides, uridine triphosphate 

 and cytidine triphosphate (78), and phospholipids 

 (217) seem necessary to maintain neurons in a func- 

 tioning state. It is of some interest that these nucleo- 

 tides, which are concerned with the synthesis of phos- 

 pholipid and of galactose and galactolipins, rather 

 than guanosine triphosphate, concerned with pro- 

 tein synthesis, have proved important. 



METABOLISM. Amount. For peripheral nerve, the energy 

 turnover per unit of protoplasm is little more than 

 that for striated muscle, but that of central nervous 

 system [70 per cent of which is due to neurons 

 1 lower); is jn to ;n limes greater perhaps to main- 

 tain the vigorous continued growth. Under maximal 

 driving conditions oxygen consumption is about 

 doubled loi nerve (85) and also brain (Sokololf), but 

 oxidative phosphorylation may be decreased (Abood). 

 The active metabolism of the nerve liber can be 

 blocked with preservation of the resting level, and 

 such a poisoned nerve can conduct for hours (31, 58; 

 see also Mcllwain for similar I dock of active metabo- 

 lism ill neurons), Ibis is reminiscenl of the convulsive 

 aciiviiv oi .1 perfused brain which proceeds with no 

 carbohydrate usage nor increased oxygen consump- 

 tion (Abood 1 , bin it is mil the same since, in the nerve, 



glucose is not even the prim.iiv fuel ol choice. It 

 should be stressed that the maintenance ol resting 

 ibolism is different qualitatively and quantita- 

 tively between nerve fiber and cell bod} and also 

 from the extra metabolism • •'' active functioning 



Fuel. Neurons have special relations to glucose and 

 to glutamic and aspartic acids. These latter are espe- 

 cially rich in brain and function in transamination, 

 related to gamma amino butyric acid — one of the 

 presumptive transmitters or modulators of inhibitory 

 impulses (247) and to potassium concentration in 

 neurons (Mcllwain). Glucose, normally the ultimate 

 fuel for neurons as a whole, is not essential for the 

 nerve fiber nor, immediately, even for the cell body. 

 Lipoprotein and nucleoprotein materials, partly in 

 microsomes, are reversibly lost during physiological 

 activity of neurons and can support such activity for 

 hours. Normally restoration is achieved via glucose 

 oxidation, but this may well be violated in von 

 Gierke's glycogen disease, in extended hypoglycemia, 

 and under conditions of artificial perfusion [compare 

 Gerard (106), Geiger (78) and Rinkel & Himwich 

 (246), as well as the chapters by Sokoloff and Abood]. 



Control. Ultimately, chemical morphology must 

 determine neuron function, and all influences upon 

 neurons must alter the number or locus of molecules 

 or ions or macromolecules of various types. The 

 locus can be altered by currents, permeability 

 changes and the like. A given cell or substructure 

 is moved from an existing steady state of equilibrium 

 only by the change of concentration of substances 

 at its surface, by diffusion from or to the surrounding 

 or the inner phase, or by migration under a newly 

 formed potential gradieni. All other events must be 

 secondary. A new substance, as a drug or hormone, 

 might reach a cell via the blood stream or, a trans- 

 mitter or metabolite, from neighboring structures. 

 Substances moved by a changed potential are ions 

 forming a current from a new source to a sink. (Only 

 in special highly structured systems, acting as semi- 

 conductors, or resonating molecules are electron 

 movements probably involved; and these are, on 

 present evidence, not primary events in neuron ex- 

 citation.) Such movements are ere. nest for small 

 mobile ions, mainly the inorganic ones and perhaps 

 some simpler highly polar — NH U or — GOOI1 or- 

 ganic ions 



But movement as such is pointless, the concentra- 

 tion of ions in any cube of volume within a homoge- 

 neous conductor is nol altered bv currenl How, for 

 equal members enter and leave it. ( )nlv where struc- 

 tural heterogeneity .\is|s, such as given bv binding 

 sii.s or a boundary ('membrane' 1 with lower perme- 

 ability to the ion in question, or .is an impermeable 

 dielectric which makes possible .1 condenser action, 

 cm the concentration of ions rise or fall. An altered 

 ion concentration, or ratio, in turn can activate or 



