CARDIAC MUSCLE CONTRACTILITY 



'75 



ternai potassium concentration falls, and that the 

 mechanism for transporting potassium into the cell is 

 stimulated by the fall in potassium. The lower the 

 potassium falls, the greater the stimulation of the 

 potassium pump, until finally the potassium influx 

 becomes equal to the potassium efflux so that a new 

 steady state is achieved in which no further fall of 

 cellular potassium concentration occurs. In summary, 

 one postulates that the potassium pump is affected 

 by the intracellular potassium content so that for 

 any frequency there is a characteristic tension, 

 potassium content, and rate of potassium transport 

 into the cell. 



Vick & Kahn (304) produced e\idence confirming 

 part of the Hajdu study by showing that a net lo.ss of 

 potassium from guinea pig heart occurred when the 

 stimulation rate was increased. Brown et al. (35) 

 observed no net loss of potassium from the hearts of 

 intact dogs when stimulation frequency was increased 

 over an approximately 2-fold range. It is possible 

 that in their preparation the cardiac muscle ''potas- 

 sium pump" was more sensitive to intracellular 

 potassium content than in the frog or guinea pig 

 heart, so that the rise in potassium efflux with in- 

 creased frequency was immediately matched by a 

 rise in influx without a significant loss of intracellular 

 potassium. The steady state potassium fluxes of dog 

 cardiac muscle do increase with stimulation frequency, 

 according to the studies of Wood & Conn (335). 



A few general comments should be made about 

 the Bowditch staircase. It is clear that any factor 

 that alters the contractile force of cardiac muscle 

 will aflfect the force-frequency relationship. In the 

 case of the frog heart there is a comparatively small 

 change in twitch tension with frequency directly 

 after the heart has been removed from the animal, 

 but after a period of several hours washing in Ringer's 

 solution the twitch tension varies greatly with 

 alterations in frequency. This is the characteristic 

 quality of the washed or "hypodynamic" frog heart. 

 High twitch tension, which does not fall when stimula- 

 tion frequency is lowered, occurs in the presence of 

 low extracellular sodium or potassium, or high extra- 

 cellular calcium. Among the most effective agents 

 for inducing a maximal twitch tension which is 

 insensitive to frequency changes over a wide range 

 are digitalis and cardioglobulin, a cardiotonic 

 protein system recently isolated from mammalian 

 blood plasma (112, 188). 



Although the stepwise changes in tension with 

 changes of frequency can be correlated with changes 

 in intracellular potassium, there is no evidence that 



the potassium change is directly responsible for the 

 altered contractility. Some authors, for example 

 (213, 2 1 8a, 289), are inclined to attribute the in- 

 creased tension of the Bowditch staircase to an accu- 

 mulation of cellular calcium, rather than a diminu- 

 tion in potassium. A net accumulation of calcium 

 with changes in stimulation frequency has not yet 

 been shown. In any case, both ions have effects on 

 the function of mu.scle. Small changes in potassium 

 concentration, for example, produce marked altera- 

 tions in the shortening of actomyosin threads. The 

 dramatic effects of calcium on muscular contractility 

 are likewise well known (see .section iv). At the 

 present time, a choice between the two ions cannot 

 be made. Furthermore it cannot be said whether the 

 variations in contractility with frequency reflect a 

 change in the milieu of the contractile protein, or a 

 change in excitation-contraction coupling. 



The biophysics of the Bowditch staircase phenome- 

 non has been investigated by Ritchie & \Vilkie (243) 

 in the case of skeletal muscle. These workers found 

 that previous stimulation of a frog sartorius caused 

 an increase in the duration of the active state (see 

 section i for a discussion of the active state), and 

 they believe that this accounts for the staircase 

 phenomenon and the posttetanic potentiation which 

 can be seen in frog skeletal muscle. On the other 

 hand, the increased twitch tension that occurs with 

 increasing frequency in cat papillary muscle has been 

 attributed to an increa.se in the intensity rather than 

 in the duration of the active state (i). 



Reverse Staircase 



The essential fact about the reverse staircase is that 

 following a twitch a comparatively long period of time 

 is required before cardiac mu.scle regains full con- 

 tractility (31, 276). This is illustrated by the curves 

 shown in figure 14 (31). Cardiac tissue was stimulated 

 at a regular frequency. Then a test pulse was given 

 at varying intervals following a normal beat and the 

 amplitude of contraction was recorded. It can be seen 

 in the experiments cited that about 5 sec was required 

 for maximum amplitude to be reached, and it is 

 likely that if isometric tension rather than isotonic 

 shortening had been measured, the plateau would not 

 have occurred until an even longer interval had 

 passed. This curve of recovery of contractility is not 

 significantly altered by variations in the previous 

 stimulation frequency over a range from 60 to r 20 

 beats per min (but it is difficult to generalize this 

 conclusion over a wide frequency range, since the 



