310 PHYSIOLOGY OF INDUCED HYPOTHERMIA 



to the slow diastolic depolarization, a slow upward curvature of the trace preceding 

 the upstroke of the action potential and a slight decrease in magnitude of the re- 

 versals^- ^^ In adjacent areas of the membrane, driven by the primary pacemaker, 

 the slow diastolic depolarization abruptly changes into the action potential upstroke 

 as propagated activity arrives at the recording site (fig. 5). Records obtained from 

 normal pacemakers in the S-A node^^ and the sinus venosus'*-' *^ and from ectopic 

 auricular pacemakers^^ all show the same time-course of potential change initiating 

 spontaneous activity. 



(c) Refractoriness. The discussion of the refractory periods of the mammalian 

 heart in the preceding paper have indicated that the recovery of excitability in 

 cardiac muscle is a complex process, perhaps even more so than in the case of nerve 

 or skeletal muscle. Although little is known of the basic mechanisms responsible 

 for refractoriness, the changes in excitability encountered during repolarization can 

 be partly explained by a consideration of the relationship between membrane po- 

 tential and the change in Na current which results from a given degree of depolari- 

 zation. Weidmann'" has studied this relationship in isolated Purkinje fibers by 

 means of the "voltage-clamp" technique.^' In this type of experiment the trans- 

 membrane potential of a given fiber is held at different steady levels of depolariza- 

 tion by means of current passed through one intracellular microelectrode and at 

 each level of membrane potential the action potential elicited by a threshold stimulus 

 is recorded by a second electrode in the same fiber. The maximum rate of rise of 

 the action potential is employed as an indicator of the magnitude of the inward 

 sodium current. 



Results obtained by this type of investigation demonstrate that there is an 

 S-shaped relationship between the steady level of meml)rane potential and maximum 

 inward sodium current. Thus, while at resting potentials greater than 90 mv the 

 rate of rise of the action potential is maximal, at a membrane potential of 70 un- 

 it has fallen to one half and at a resting potential of 50 mv it is less than ten per 

 cent of maximum. This relationship is seemingly responsible for the inability of 

 the fiber to respond to maximal stimuli during the absolute refractory period, since 

 if there is no inward sodium current there can be no action potential. Furthermore, 

 the same property of the membrane can explain in part the elevated thresholds en- 

 countered during the relative refractory period. During repolarization, when the 

 transmemljrane potential is low, a stimulus of normal intensity results in only a 

 small depolarization ; this depolarization, in turn, causes only a negligible change 

 in Na permeability and an action potential fails to occur. Stimuli much stronger 

 than threshold, on the other hand, result in a large depolarization and the maximum 

 Na current of which the membrane is capable at that instant. When this current 

 density is adequate, a propagated action potential is formed. As repolarization ])ro- 

 ceeds toward completion, progressively smaller depolarizations result in i)ropagated 

 action potentials. It is also likely that part of the re(|uiremcnt for increased stimulus 

 intensity during the relative refractory period is caused l)y the net outward currt-nt 

 (possibly carried by K ) wliich is responsible for rei)olarization of the membrane. 

 This current ()pi)o.ses the depolarizing effect of the stimulus and raises the reiiuire- 

 ment for stimulus current. 



The temporal relationshi]) between the transmembrane action potential of ventric- 

 ular muscle and the excitability of the membrane to ai)plied stinuili can be sum- 



