460 ANNALS NEW YORK ACADEMY OF SCIENCES 



with solutions containing from about 70 mM to 10 mM calcium chlo- 

 ride, there is a certain degree of irritability corresponding to each con- 

 centration. This is measured as the minimal strength of current nec- 

 essary to initiate a conducted impulse. It may be thought of as an 

 index of the stability of the excitable portion of the nerve structure. 

 We shall subsequently refer to the fact that the rate of oxygen con- 

 sumption of nerve is also modified by changes in its calcium content. 

 Here, it is pertinent to remark that the variations of oxygen consump- 

 tion occur within this same range of calcium concentrations in which 

 there are measurable changes of irritability. In the case of frog nerve, 

 moderate increases in calcium above 2.0 mM do not cause a further 

 appreciable decrease of irritability nor a further decrease of oxygen 

 consumption. At very much higher concentrations, above 15 mM, 

 the irritability again decreases,^ and there is a further fall in the oxygen 

 consumption.* If the concentration of calcium be lowered beyond 0.3 

 mM, or 10 mM in the case of squid nerve, it is no longer possible to 

 measure the irritability in terms of the strength of current necessary to 

 initiate an impulse. At these levels, the nerve structure has been so 

 much modified, its stability lowered so much, that it goes through 

 periodically-recurring cycles of change, with consequent, self-initiated 

 trains of propagated impulses.^ 



II 



The response of nerve to the exciting action of an electric current 

 can be studied in a nerve trunk or in a bundle of fibers. The stimulus 

 is under the control of the experimenter, and all of the fibers are ex- 

 cited simultaneously. Accordingly, the action potential recorded from 

 the aggregate of fibers of a given type is a fairly accurate representa- 

 tion of the sequence of events in each fiber, provided temporal disper- 

 sion, due to differences in conduction velocity, is avoided. 



The situation is quite different in the case of chemical excitation. 

 The altered chemical environment modifies the properties of the fibers, 

 so that a sequence of cychc events develops in each fiber, with a fre- 

 quency that is determined by the characteristics of the fiber. Because 

 these intrinsic characteristics differ, the frequency of the impulses dis- 

 charged from a chemically treated region varies from fiber to fiber. 

 Furthermore, the properties of the fiber may change from moment to 

 moment, so that the sequence of impulses is not truly periodic. Finally, 

 the times of initiation of impulses in one fiber are independent of the 

 timing of these events in the other fibers, in contrast to the externally 

 determined synchronization imposed by electric stimuli. Because of 



