CARDIAC MUSCLE CONTRACTILITY 



l6l 



lOOmsec 



50- 



100- 



THRESHOLD POTENTIAL 1 '0 f. 



600 



200 



40 



60 80 



100 120 



0-5 -1 



FIG. g. Diagrammatic cardiac action po- 

 tential curve. Resting potential, 90 mv. Small 

 local depolarizations are not followed by a 

 spike. Depolarization by an amount ^i or more 

 causes typical propagated response, consisting 

 of spike and 3 phases of repolarization. Phase i : 

 rapid early repolarization; phase 2: plateau; 

 phase J.- terminal repolarization. 



FIG. 10. Effect of calcium ions on the rela- 

 tionship between membrane "clamp" potential 

 and maximal rate of rise of the action po- 

 tential. Open circles correspond to values ob- 

 tained before, filled circles to values measured 

 after the application of a calcium-rich solution. 

 [After Weidmann (314).] 



FIG. II. Relation between calcium concen- 

 tration in bathing iiuid and peak tension of iso- 

 metric twitches of isolated frog ventricle. 

 [After Niedergerke (220).] 



The effects of chang;ing potassium on the electrical 

 events associated with excitation can best be appre- 

 ciated after revievvinsj; one or two facts about trans- 

 membrane potentials and excitability. Reference to 

 figure 9 will show that in order to achieve a propa- 

 gated depolarization it is necessary to decrease the 

 resting potential to a given \alue, the so-called 

 threshold potential. Depolarizations to less than this 

 value result in small local changes but no propagated 

 depolarization. The second point, which is illustrated 

 by figure 10, shows the relationship between the 

 rising velocity of the action potential and the level of 

 the previous resting potential as determined by 

 Weidmann (314) on Purkinje fibers using a voltage 

 clamp technique. It can be seen that as the steady 

 level of membrane potential is lowered, the rate of 

 rise of the action potential, which is thought to be 

 due to the rate of inward movement of sodium 

 current, falls until it reaches a value close to zero at 

 a resting potential of about 60 mv. Thus, below 

 resting membrane potentials of 60 mv in this experi- 

 ment there is no inward sodium current and therefore 

 no action potential. Returning to the effects of 

 potassium, it can now be appreciated that any change 

 in [K]o that leads to a decrease in resting membrane 

 potential will cause first an increase in excitability 

 and then an abrupt decrease. The phase of increased 

 excitability occurs in the region in which the resting 

 membrane potential is reduced but is still greater 

 than the threshold potential. At such values a smaller 



low concentrations of potassium can be eliminated by lowering 

 the calcium concentration below normal levels. The latter 

 effect would not seem to be a phenomenon related to the con- 

 tracture which may occur in very low potassium solutions in 

 which calcium concentration is normal since the effect is also 

 observed in the nonmuscular Purkinje fibers. 



than normal current is required to reach the threshold 

 potential. Spontaneous rhythmicity, which is seen 

 with increased concentrations of extracellular potas- 

 sium, can be explained by depolarization of the 

 resting membrane to potential levels close to the 

 threshold potential. 



When, on the other hand, the level of the resting 

 potential has reached the threshold or lower, it is 

 clear from reference to figure 10 that no sodium 

 current and therelore no propagated depolarization 

 can occur. The observed effects of increased potas- 

 sium on the action potential, such as a diminution in 

 the rate of rise of the action potential and a lower 

 than normal height of the spike, are probably due to 

 resting membrane depolarization with the associated 

 changes just described. The diminution in conduction 

 velocity caused by increased potassium is a reflection 

 of the slower rate of rise of the action potential. 



Effects of Sodium and Potassium on Conlractilitv 



It is generally accepted that alterations in the 

 extracellular concentrations of .sodium or potassium 

 may be associated with changes in contractilitv of 

 heart muscle. Ringer (242) showed that increasing 

 potassium caused a decreased contractile response of 

 the isolated frog heart, and it has since been demon- 

 strated that the opposite effect can be produced by 

 decreases in the concentration of extracellular potas- 

 sium (47, 62, 1 10). Variations in extracellular sodium 

 concentration are associated with similar changes, 

 the basic facts having been summarized as early as 

 1920 by Daly & Clark (62), who stated that '"lack of 

 potassium or sodium and excess of calcium all 

 produce increase of systolic tone in the heart." 

 The alterations in contractilit\- caused bv such inter- 



