CARDIAC MUSCLE CONTRACTILITY 



l6- 



fashion somewhat comparable to solutions of potas- 

 sium chloride (260 and references cited therein). On 

 the other hand, rubidium cannot be substituted for 

 potassium in the animal economy, and if rats, for 

 example, are fed diets in which potassium is replaced 

 by rubidium death occurs after several weeks (241). 

 Examination of such animals before the terminal 

 stages of the experiment shows that although plasma 

 rubidium concentration is lower than that of potas- 

 sium, muscle rubidium is higher than potassium; 

 the ratio of intracellular to extracellular potassium 

 concentration is about 44, that for rubidium is 118. 

 And indeed in cesium-fed animals the ratio is 185. 

 Relman ct at. (241) used these findings as evidence 

 against the idea that the distribution of muscle 

 potassium was determined solely by its electrochemical 

 potential gradient without the contribution of any 

 active transport. Clearly the distribution of rubidium 

 across the cell membrane could not be explained 

 in this fashion, and could come about only by virtue 

 of active rubidium uptake or binding of rubidium 

 by muscle tissue. Further light on this problem was 

 provided by the studies of Lubin & Schneider (198), 

 who showed that if muscles which had been depleted 

 of potassium in the cold were transferred to solutions 

 at room temperature containing equal concentrations 

 of rubidium and potassium, a net accumulation of 

 rubidium greatly in excess of potassium occurred 

 over a period of 3 hours. Such results could be ex- 

 plained a) by assuming rubidium binding by the 

 muscle, or b) by assuming that muscle transported 

 both rubidium and potassium actively across the 

 membrane into the cell, and that pa.ssive rubidium 

 efflux was much lower than that of potassium, or c) by 

 assuming that active influx of rubidium was much 

 greater than that of potassium. Experiments by 

 Lubin & Schneider (198) and also by Sjodin (277) 

 showed that permeability of the cell membrane of 

 frog sartorius muscle for rubidium was much less 

 than that for potas.sium. Lubin and Schneider's 

 conclusion was based on efflux of tracer potassium 

 and rubidium from muscle at zero degrees under 

 conditions in which active transport was minimal. 

 Sjodin's findings were based both on membrane 

 potential measurements and also on flux measure- 

 ments. Sjodin also found that if a muscle was placed 

 in a solution containing rubidium ions at a concen- 

 tration of 100 mM per liter, an immediate drop in 

 membrane potential from a normal of 75 to approxi- 

 mately 45 mv was observed, and then the membrane 

 potential declined progressivelv over the next 7 

 hours to a level of about 15 mv. Tlie initial depolar- 

 izing action of rubidium is due to the addition of; a 

 new cation to whicli the muscle membrane is to 



some extent permeable. [For a quantitative treat- 

 ment based on the Goldman constant field equation, 

 see (277).] The subsequent progressive decline in 

 membrane potential is due to the slow accumulation 

 of rubidium and loss of potassium. 



The peculiar actions of rubidium are perhaps most 

 simply explained, then, by postulating a membrane 

 transport mechanism which distinguishes poorly, if 

 at all, between rubidium and potassium, so that 

 both rubidium and potassium are accumulated 

 actively. This fact, combined with the observed much 

 lower cell membrane permeability coefficient for 

 rubidium than for potassium, will result in a net 

 increase in intracellular rubidium to concentrations 

 exceeding that of potassium. Such is the case for frog 

 skeletal muscle, but the results should not be extra- 

 polated freely to other tissues. Whereas the data on 

 frog skeletal muscle strongly indicate that the rubi- 

 dium permeability coefficient is considerably smaller 

 than that for potassium, studies of Love & Burch 

 (194) indicate that this great difference does not 

 exist for human red blood cells, in which rubidium is 

 concentrated to the same extent as potassium. Thus 

 the use of Rb*" as a "tracer" for potassium may be 

 justified for red blood cells, but would obviously not 

 reflect the behavior of potassium in skeletal muscle. 

 No careful studies exist at the present time to show 

 where cardiac muscle fits into this picture. 



IV. CALCIUM 



Effect of Calcium on Contractilitv 



It has been known for many years that cardiac 

 contractility is markedly influenced by variations in 

 calcium concentration. Ringer in 1883 observed 

 that the contractions of the isolated frog heart 

 disappeared in a calcium-free salt solution and were 

 restored by the addition of calcium. He also noted 

 that a further increase in calcium concentration 

 "rounds the top, and also broadens the trace of the 

 beat." The effect of calcium on the staircase phenome- 

 non was observed by Moulin & Wilbrandt (213), 

 and Hajdu (iiia), and are described in section vi. 

 The relationship between twitch tension and external 

 calcium concentration at a given frequency of stimu- 

 lation has been examined recently by several investi- 

 gators. A curve for isolated frog heart is shown in 

 figure 1 1 . A comparable curve for frog ventricle was 

 obtained by Payne & Walser (230). The relationship 

 for mammalian heart muscle obtained bv Reiter 

 <■/ al. (239, 240) is similar, except that there is no 



