CARDIAC MUSCLE CONTRACTILITY 



167 



plateau phase, but the rate is slower than that of the 

 rapid repolarization (phase 3) which normally 

 follows the plateau. Low calcium has the opposite 

 effect in that the plateau of papillary muscle becomes 

 increased in duration, but the terminal repolarization 

 phase is not altered. In the complete absence of 

 calcium and magnesium a remarkable prolongation 

 of the plateau to durations as long as several seconds 

 has been observed in both auricular and papillary 

 muscle. A phenomenon which may be related to this 

 was observed by Garb (83), who found that with 

 calcium concentrations of less than 0.27 mM per liter 

 the presence of strontium chloride in concentrations 

 not exceeding 10 mM per liter was associated with a 

 great prolongation of the RT interval of the electro- 

 gram of his cat papillary muscle preparation. The T 

 wave under these circumstances was often inverted 

 but not widened. It appears then that as in the case 

 of the calcium- and magnesium-depleted prepara- 

 tions the effect here was to cause a great prolongation 

 of the plateau without any significant change in the 

 rate of repolarization when it finallv occurred. Brooks 

 et al. (34) have suggested that the strontium in this 

 low calcium experiment displaces tissue calcium 

 from sites in the fiber membrane essential for normal 

 repolarization. 



Exposure of cardiac tissue to very low concentra- 

 tions of calcium may cause a transient increase in 

 excitability followed by a decrease to the point of 

 complete loss of propagated responses in spite of a 

 normal resting potential (149). The maximum rate 

 of rise of the action potential is decreased b\- low 

 extracellular calcium concentrations. 



In summary, it is clear from the above discussion 

 that calcium is most important for the normal 

 function of the excitable membrane. Although it has 

 little effect on the resting membrane potential under 

 normal conditions, it does modify resting potential 

 changes induced by alterations in extracellular 

 potassium concentration (see footnote 7). The most 

 important actions of calcium on electrical events, 

 however, are on excitability, spike, and repolarization 

 phenomena as described in the preceding paragraphs. 



Chemical State of Calcium in Living Tissue 



There are few reliable measurements of calcium 

 ion concentration in mu.scle. Fenn ct al. (76) reported 

 a value of eg mM per kg of fiber water for cat and 

 rat striated muscle. The fiber water calculations were 

 based on a chloride space measurement of extra- 

 cellular fluid. Gilbert cS; Fenn (92) ha\'e shown that 



the calcium content of muscle varies widely, accord- 

 ing to the condition of the tissue. They found that 

 the calcium concentration of freshly dissected frog 

 sartorius muscle was i .63 mM per kg, but increased 

 to 2.84 mM per kg after a short period of immersion 

 in Ringer's .solution. An even greater deviation from 

 the freshly dissected tissue value was found if the 

 muscle was cut into small pieces, the concentration of 

 calcium in this muscle being about twice that of the 

 controls immersed in Ringer's solution. These investi- 

 gators coitcluded that dead or damaged tissue takes 

 up calcium from the surrounding medium. Measure- 

 ments of calcium concentration in other tissues 

 include a value reported by Keynes & Lewis (172) of 

 0.5 mM per kg for squid axoplasm, extruded from 

 the nerve sheath to eliminate the surface membrane 

 and connective tissue. These authors found calcium 

 concentrations of i mM per kg in rabbit blastocytes. 

 The value of 9.0 mM per kg reported by Sekul & 

 Holland (267) for rabbit atria obviously requires 

 some explanation in the light of the above values for 

 other tissues. Since the atria had been soaked in 

 Ringer's solution, it is possible that the soaking and 

 also the contribution of the cut edges of the atrium 

 accoimt for the high calcium measured. The large 

 fraction of connective tissue in atrium is probably 

 another factor, as will become clear from the discus- 

 sion below. 



Recent studies on tiie kinetics of radioacti\e calcium 

 mo\ement in isolated tissues have thrown light on the 

 distribution of calcium among the various phases of 

 tissue. It was found by Niedergerke (220), for example, 

 in efflux experiments on strips of frog ventricle, which 

 had been soaked for 1 2 hours in radioactive calcium, 

 that calcium efflux could be divided into two parts, a 

 rapid phase occurring during the first 30 min, and a 

 second phase presumed to represent intracellular 

 radioactive calcium which was released from the 

 cell very slowly. The rapidly moving radioactive 

 calcium which was lost in the first 30 min of soaking 

 in nonradioactive solution amounted to 1.37 mM 

 per kg of tissue. This was three and one-half times 

 the amount expected in the heart extracellular fluid, 

 assuming the extracellular phase to be 25 per cent 

 of the tissue volume. These results suggested that the 

 rapid phase calcium represented not only the tracer 

 distributed in extracellular fluid, but also a moiety 

 bound to connective tissue or to a surface site of the 

 heart muscle cell from which it could exchange 

 readily with the surrounding medium. A more 

 quantitative approach to this problem in frog sartorius 

 muscle has been made h\ Gilbert & Fenn (92) by 



