GERARD: NERVE METABOLISM AND FUNCTION 579 



endure for minutes. Conduction fails when respiration^' ^^ or gly- 

 colysis^^ is disturbed, although, whether this is a result of interference 

 directly with active metabolism, or is secondary to interference with 

 resting metabolism, is not clear. •" A mechanism, partly in terms of 

 phosphate intermediates, for insuring the one-to-one relation between 

 early and late events, was suggested some time ago-° and is still useful. 

 But, before pursuing this aspect, what of conduction itself? 



Depolarization 



Electric currents, applied to nerve or muscle, excite at the cathode, 

 where ion movements are such as to depolarize the polarized mem- 

 brane. The most direct evidence for the preexisting membrane poten- 

 tial and for its diminution by trans-membrane currents is that from 

 impaled single ncrve"^' '^ and muscle fibers. ^^ Membrane potentials 

 up to £0 mV. have been obtained from resting units; and excitation 

 is easily achieved with a cathode outside and anode inside the fiber, 

 but even 100- fold greater currents in the reverse direction are ineffec- 

 tive. Further, recalling the uniquely high sensitivity of these tissues 

 to electric currents and the generation of electric changes when non- 

 electric stimuli are applied, it seems probable that membrane depolar- 

 ization by ion movements is the initial step in all forms of natural 

 excitation of nerve and muscle. AVhether excitation results most di- 

 rectly from a potential, impedance, or other, change, and to what crit- 

 ical level, is a separate and secondary problem. 



Active Membrane Participation 



There is much evidence that the nerve membrane does not passively 

 follow the imposed depolarization, at least when applied currents are 

 more than a few per cent of threshold, but responds with active changes. 

 These changes are almost certainly chemical as well as physical. The 

 decreased impedance is suggestive, but perhaps not convincing, on this 

 point. The existence of prepotentials (with depolarizing shocks, but 

 not with equal ones in the reverse direction) in invertebrate^*- ^^ and 

 vertebrate nerve^^ has been several times referred to in this publication. 

 The fact that these often oscillate, and that the oscillations can incre- 

 ment without additional external change,-* has been emphasized here 

 by the report of Bronk and Brink, and by Cole's discussion. The oscil- 

 lation period, 4 to 5 msec, observed in Ca-depleted nerves (Bronk), 

 fits satisfactorily with the physical constants of the membrane, men- 

 tioned by Curtis, which should lead to resonance at about 250 cycles 

 per sec. But such physical factors control only the period of oscilla- 



