CARDIAC MUSCLE CONTRACTILITY 



163 



ion sensitivity than isolated actomyosin preparations. 

 However, experiments with the isolated protein and 

 with glycerinated fibers prepared by certain investi- 

 gators seem to show that the contractile mechanism 

 may be quite sensitive to small alterations in the 

 ionic environment. The variability of results with 

 glycerinated fibers emphasizes the need for careful 

 attention to detail in the preparation of the material. 



The action of monovalent cations on heart muscle 

 contractility has been viewed in another fashion by 

 VVilbrandt & KoUer (324) and by Liittgau & Nieder- 

 gerke (200). These investigators re-examined the 

 antagonism between calcium and the monovalent 

 cations with respect to contractility and found that 

 the results of a large number of experiments, in which 

 bathing fluid, calcium, and sodium concentrations 

 were varied independently over a wide range, could 

 be expressed in a single curve obtained by plotting 

 contractile force (as percentage of the maximum) 

 against the ratio [Ca] [Na]-. This finding lends 

 credence to the idea that the opposing actions of 

 calcium and sodium occur at the same locus. Further- 

 more, despite the barriers to diffusion which calcium 

 apparently encounters in the cell interior (see section 

 iv), changes in calcium concentration in the bathing 

 medium aflfect twitch or contracture tension very 

 rapidly. It would therefore seem reasonable to 

 postulate that the action of calcium (and sodium) 

 occurs at a rather superficial site in the muscle on a 

 link in the excitation-contraction chain rather than 

 on the actomyosin directly. Liittgau & Niedergerke 

 (200) have, in fact, postulated that contraction is 

 initiated by a calcium complex which moves from a 

 surface site into the cell interior when the cell mem- 

 brane is depolarized. According to their view, sodium 

 ions can displace calcium from this complex, rendering 

 it inactive. The increased calcium influx observed in 

 the absence of extracellular sodium ion or under 

 conditions of membrane depolarization is adduced 

 as supporting evidence. 



Their theory as originally presented seems to leave 

 little room for the role of changes in potassium con- 

 centration on contractility. They believe that sodium 

 is attracted to the anionic portion of the surface site 

 calcium complex, but that potassium is probably not. 

 In fact they suggest that the anionic moiety can 

 even distinguish between sodium and lithium, since 

 twitch or contracture tension is increased not only in 

 sodium-free sucrose solutions but also in .sodium-free 

 lithium solutions, the lithium thus not being a 

 substitute for sodium with respect to muscle con- 

 tractility. The difference between sodium and 

 lithium, however, may be explained on another 



basis (see section in), according to which the lithium 

 ion never reaches the complex in short-term experi- 

 ments, and therefore no conclusion can be drawn 

 about the affinity of lithium for the complex. 



In general, although the evidence suggests that 

 calcium ions can affect contractility by an action on 

 a relatively superficial muscle site (see section iv), 

 the idea that .sodium, specifically among the mono- 

 valent cations, has an antagonistic action at this 

 locus needs further support before it can be accepted. 



III. OTHER .-^LK.^LI METAL IONS 



Lilhiiim 



Lithium is the lightest member of the alkali metal 

 group. Although the ionic radius of lithium in crystals 

 is the .smallest in the group, it should be noted that 

 the radius of the hydrated lithium ion is the largest 

 among the alkali metal ions. Traces of lithium are 

 found in mammalian organs, but no physiological 

 role for this ion has been established. Biochemically, 

 lithium bears some resemblance to its congener 

 sodium. For example, lithium and sodium have no 

 effect on, and may inhibit, a group of enzymes that 

 require potassium for activity (265, 268). Since 

 lithium is clearly distinguished from potassium at the 

 enzymatic level, it is not surprising to find that 

 cellular accumulation of lithium results in marked 

 derangements of cellular function. It has been 

 found by Mudge (214), for example, that substitution 

 of lithium for sodium in the bathing fluid of potassium- 

 deficient kidney cortex slices is associated with a 

 marked inhibition of potassium uptake and also 

 with a 30 to 40 per cent inhibition of respiration. 

 Likewise, OrlofT & Kennedy (227) have found that 

 lithium interferes with acidification of the urine, 

 and Taggart et al. (294) have reported that para- 

 amino hippurate uptake by kidney slices was inhibited 

 by lithium. Further examples of the toxicity of 

 lithium can be found in the review by Schou (265). 



The action of lithium on cells has been elucidated 

 by studies on striated muscle and on nerve, a brief 

 review of which will provide a basis for understanding 

 the effects of this ion on cardiac tissue. In 1902, 

 Overton (228) showed that the ability of frog striated 

 muscles to conduct impulses and contract was 

 alwlished if the sodium ion in the bathing medium 

 was replaced by sucrose. The only other cation which 

 could maintain or restore excitability was lithium. 

 If the lithium concentration was 35 mM per liter or 

 less, no impairment of muscle function was observed 



