CARDIAC MUSCLE CONTRACTILITY 



171 



when placed in a calcium-free solution gradually 

 regains this as calcium ion diffuses from the cell 

 interior outward. Replacement of the bathing solu- 

 tion by another calcium-free solution causes disap- 

 pearance of contractility again, so that the process is 

 not some sort of accommodation independent of 

 calcium ion. The rapidity with which calcium ion 

 increased contractility in the turtle heart in the 

 experiment by Weidmann, cited earlier (.see first of this 

 section), al.so showed that contractility can be influ- 

 enced by calcium acting on a relatively superficial 

 site of the heart muscle. The prompt release of Ca*^ 

 from frog sartorius muscle following a 1 2-sec stimula- 

 tion shows that contraction is associated with the 

 mobilization of a superficialK- located calcium moiety 



(273)- 



Ail these pieces of evidence are consistent with the 

 idea that at least one link in the excitation-contraction 

 cycle is calcium-sensitive. It has been suggested by 

 some investigators that initiation of contraction is 

 actually mediated by calcium, or a calcium complex 

 moving from a superficial locus into the cell interior 

 (16, 200, 213). In the case of heart muscle, if the 

 amount ot calcium at this locus influences contractil- 

 ity, then it must change readiK- with changes in 

 extracellular calcium concentration to which cardiac 

 contractility is so sensitive." It will be of interest to 

 determine whether the increased calcium influx 

 associated with stimulation (267, 328) varies with 

 contractile force and with changes in the concen- 

 trations of extracellular calcium. 



V. OTHER ALKALI EARTH METAL IONS 



Magnesium 



Magnesium ions block neuromuscular transmission 

 in concentrations which do not stop nerve conduction 

 or the response of muscle to direct stimulation. This 

 action of magnesium may be reversed by increasing 

 calcium ion concentration. The widespread effects of 



' Skeletal muscle is different in this regard. Exposure to 

 calcium-free solutions is associated with a drop in twitch tension 

 only after a period of several hours. If calcium concentration is 

 raised above normal, resting calcium influx is increased, but the 

 extra calcium influx associated with contraction is not increased. 

 The superficial calcium identified by Shanes and Bianchi, which 

 is lost readily to the surrounding medium (see table i ) is thus 

 not important for skeletal muscle contractility. If a superficial 

 moiety of calcium is involved in the e.xcitation contraction cycle 

 of skeletal muscle it must be part of the calcium which 

 exchanges slowly in the resting state. 



magnesium on the whole organism are summarized 

 in a recent review by Engbaek (71). 



The intravenous injection of magnesium salts into 

 intact animals is followed by a progression of electro- 

 cardiographic abnormalities which have been studied 

 by Smith and co-workers (279). As the serum con- 

 centration of magnesium rises from 2 to 5 meq per 

 liter, there is an initial tachycardia which is followed 

 shortly by bradycardia. There are extensive disturb- 

 ances of intracardiac conduction, including a) 

 progressive increase in P-R interval at 5 to 10 meq 

 per liter magnesium; b) occasional S-A and A-V 

 block of various grades, occurring above 1 5 meq per 

 liter; and c) prolonged intraventricular conduction 

 time (widening of QRS interval) beginning at concen- 

 trations of 5 to to meq per liter. The final event is 

 cardiac arrest, at levels usually between 27 and 44 

 meq per liter. 



Studies on isolated cardiac tissues also reflect the 

 electrical disturbances caused by magnesium. The 

 spontaneous beating of the frog ventricle can be 

 stopped by the application of magnesium chloride, 

 though the heart is said to remain responsive to 

 mechanical or electrical stimulation (39, 210). The 

 effect of magnesium on the spontaneous rhythm can 

 be reversed by increasing calcium concentration (39). 

 It should be noted that the magnesium concentration 

 in these experiments was very high, being 64 meq per 

 liter in the protocol presented by Burridge (39), and 

 it is surprising that any response could be induced 

 under the.se conditions. Action potentials of nerve 

 fibers disappear completeU in isotonic magnesium 

 chloride ( loi ). 



Alterations in magnesium concentration do not 

 have any striking effect on isolated cat papillary 

 muscle, a tissue which is not characterized by spon- 

 taneous rhythmicity. For example. Garb (83) 

 studied both magnesium-free .solutions and 10 times 

 the normal concentration of magnesium, and in 

 neither case did he ob.serve any effect on the surface 

 electrogram of cat papillary muscle. In a study on 

 the effects of various cations on cat papillary muscle 

 excitability, Greiner & Garb (103) found that both 

 calcium and magnesium decreased excitability in 

 high concentrations, the effect of magnesium being 

 less than that of calciuin. Hoffman & Suckling (149), 

 working with a similar preparation, found a slight 

 drop in excitability at very high levels of magnesium. 

 However, if the calcium was reduced, a 5-fold increase 

 in magnesium concentration caused a shortening in 

 the plateau of the action potential in a manner 



