CARDIAC MUSCLE CONTRACTILITY 



169 



TABLE 3. Ca*^ Influx* of Resting Tissue 



Tissue 

 Frog ventricle 

 Rabbit atrium 

 Guinea pig atrium 

 Squid axon 

 Frog sartorius 

 Frog sartorius 



Reference Influx 



(221) Slow, no quantitation 



(267) 0.024 pmoles/cm-/sec 



(338) 0.015 pmoles/cmVsec 



(146) 0.076 pmoles/cmVsec 



(16) 0.094 pmoles/cmVsec 



(92) 0.8 mM/liter/hr 



* Influx into cell, based on analysis of the slow component 

 of Ca" flux. 



to eject, by some kind of actUe transport, calcium 

 which passes the membrane barrier. 



Movements of Calcium In and Out of Cells 



CELLS AT REST. It has becii observed for a variety of 

 tissues bathed in artificial media that the entry of 

 calcium into the interior of the tissue cells is extremely 

 low. This can be appreciated by reference to table 

 2 which shows the percentage equilibration of Ca''^ 

 in the tissue after long periods in radioactive calcium 

 solution. [The in vivo results of Cosmos (57) will be 

 discussed below.] It should be noted that certain of 

 the investigators in this group found an upper limit 

 to the specific activity of Ca''° achieved in tissue and 

 concluded therefore that a portion of the intracellular 

 calcium was nonexchangeable with the external 

 calcium. Information on Ca^" influx for resting 

 tissue is presented in table 3. The most complete 

 data are those of Hodgkin and Keynes, and since 

 their measurements were made on axoplasm extruded 

 from squid nerves these values are unique in repre- 

 senting direct measurements of intracellular content 

 in contrast to values derived by analysis of the slow 

 component of Ca''^ influx or efflux curves. One fact 

 which emerges from the squid axon data is the 

 extremely low permeability of the resting membrane 

 to calcium, the apparent permeability coefficients 

 of potassium, sodium, and calcium being in a ratio of 

 1 : 0.025:0.001. 



CELLS DLiRiNG ACTIVITY. Calcium movement during 

 stimulation under normal conditions. It had been shown 

 several years ago that no change could be observed 

 in the total calcium concentration of striated muscle 

 following a prolonged period of stimulation (76). An 

 increased exchange of calcium between active muscle 

 and a Ca'*^ labeled environment was demonstrated 

 by Cosmos (57), who showed that specific activity of 

 calcium in stimulated muscle was greater than that 

 of corresponding control muscles between the 3rd 

 and 4th hours of a prolonged experiment in which 



the experimental muscle was stimulated for a total 

 period of 6 hours. The curious feature of these 

 results, however, was that between 4 and 6 hours the 

 specific activity of the control muscles increased 

 and reached the level of the experimental muscles, 

 leveling off to a value of about 45 per cent exchange. 

 The most significant aspect of Cosmos' work is the 

 finding that in contrast to the apparently nonex- 

 changeable moiety of tissue calcium found in experi- 

 ments with muscles in vitro, if the radioactive calcium 

 was injected into the wliole animal and the muscles 

 were analyzed at intervals thereafter, it was found 

 that all the muscle calcium exchanged with the isotope 

 after 6 to 10 hours in the case of frogs stimulated to 

 jump, and within a period of about 2 hours in the 

 case of spontaneously active rats (see table 2). 



There is general agreement that Ca^° influx in- 

 creases as a result of stimulation. This has been shown 

 for guinea pig atrium, rabbit atrium, frog sartorius, 

 and squid nerve (16, 146, 267, 328). However, there 

 is no agreement on the question of changes in calcium 

 efflux during stimulation. Woodward (338) and 

 Shanes & Bianchi (273) having demonstrated an 

 increased efflux for frog sartorius, other authors 

 having found no change (120, 146, 267). In \iew of 

 the increased Ca''^ specific activity equilibration 

 during mu.scular activity demonstrated by Cosmos 

 (57) and the agreement that Ca''^ influx increases 

 with stimulation, one should expect a corresponding 

 increase in efflux o\er long periods of stimulation 

 if the muscle approaches a steady state with respect 

 to calcium ion exchange. 



Calcium flux during stimulation under abnormal condi- 

 tions. Before discussing this topic it would be well to 

 emphasize certain points elucidated in previous 

 sections. It was pointed out that most of the cellular 

 calcium is bound and there must be a very low 

 concentration of free ionic calcium within the cell. 

 The electrochemical gradient for calcium strongly 

 favors movement of the ion from bathing fluid into 

 the cell, and this gradient is maintained by a low 

 membrane permeability to calcium and by some 

 kind of active process for ejecting calcium. In general, 

 then, changes in calcium influx may occur because 

 of alteration in the electrochemical gradient or 

 change in membrane permeability; and changes in 

 efflux will reflect a change in the active ejection of 

 calcium, either because of an alteration in the 

 amount of calcium made asailable to the transport 

 mechanism or a variation in the activity of the 

 mechanism itself. It should be remembered that since 

 there are doubtless several different moieties of bound 



