580 ANNALS NEW YORK ACADEMY OF SCIENCES 



tion, and cannot supply the energy to maintain, even less to increase, 

 it. Energy, presumably liberated from metabolic events, must supply 

 the drive, while physical conditions only modulate its flow. The analogy 

 used in connection with the similar problem of electric oscillations in 

 the isolated frog brain-' may be used again. Air pressure, from the 

 motor, drives most windshield wipers, and their beat does rise and 

 fall with this; but the beat is much more under the control of a valve, 

 which determines when each stroke is tripped off. 



Another set of facts bespeaks, even more strongly, the intervention 

 of a chemical step this early in the excitation process. In tortoise 

 auricle,^^ crab nerve, 2*^ and even frog nerve--' (see also Gerard,^" and 

 following discussion), an opposed electric shock, delivered between a 

 supra-threshold shock and the start of the resulting propagated re- 

 sponse, can nullify the response. While it may be possible for the 

 purely physical changes, produced by a pulse in an appropriate network, 

 to surge on to a peak after the pulse has passed (as Curtis suggested 

 in connection with the reversed action potential), such a physical in- 

 terpretation is under the burden of offering positive evidence in the 

 case of the cooled auricle, where a reverse shock given 20 msec, after 

 an effective one is still able to abort the response. 



The Discontinuous Response 



When the local membrane changes have progressed sufficiently, a full- 

 fledged action appears and propagates. This response, as several 

 speakers have emphasized, is not a continuation of the earlier processes, 

 but a new and explosive group of events. Here, even more surely than 

 in the preceding phase, chemical as well as physical changes are in- 

 volved. The resting membrane potential shifts abruptly, not merely 

 toward or to neutrality, but to an inverted magnitude which can much 

 exceed the original level. ^^' "> ^^ Perhaps, as Curtis suggests, this is 

 only a physical overshoot, rather than a newly-developed, oppositely- 

 oriented, and chemically-active membrane battery; but the burden of 

 proof seems to be clearly on the adherents to such a physical view. 

 Cole's comment, that the reversed action potential can vary in mag- 

 nitude independently of the resting potential, certainly favors more 

 the positive conclusion. Hober's suggestion, that a fatty acid is re- 

 leased by activated lecithinase and, reaching the inside of the mem- 

 brane, reverses its potential, just as caproic acid does when placed 

 on the outside, is an example of the chemical, active-membrane-change 

 viewpoint. (This particular example is not fully satisfying, however; 

 for, if the non-polar chains enter the membrane lipids and the polar 



