EFFECTS ON TISSUE FUNCTION 315 



EFFECTS ON TISSUE FUNCTION 



Very little investigation of the effects of maleate on cellular activity 

 has been done, the exception being the work on renal function to be dis- 

 cussed in the next section. Surprisingly sparse are the reports on the 

 response of muscle to maleate. Kuschinsky and Liillmann (1954) observed 

 that maleate at 1.7-8.6 mM causes a prolonged contracture of the diaphragm 

 as do various SH reagents, and Hasselbach (1953) stated that 50 mM mal- 

 eate inhibits the relaxation of glycerinated muscle fibers. Even less has 

 been done on the heart and we find only that maleate and fumarate both 

 depress the isolated frog heart, the former more strongly and less reversibly 

 (Lipschitz and Hertwig, 1921). Inasmuch as I know of no other published 

 study of the effects of maleate on cardiac muscle, some preliminary ex- 

 periments may be mentioned (Webb and Hollander, 1958). Maleate at 

 5 uiM causes a 20% depression of the contractility of rat atria, and at 

 15 mM the depression is 35% within 30 min, while both the resting and 

 action potential magnitudes are reduced moderately without significant 

 alteration of the depolarization and repolarization rates. The lack of a 

 shortening effect on the action potential duration was unexpected, since 

 this is a common property of metabolic inhibitors, and it probably in- 

 dicates that not enough maleate penetrates into the myocardial cells to 

 affect the cycle. The rate at which the depression develops is very rapid, 

 so as to lead one to suspect an action on the cell membranes. Rjabinovskaja 

 (1939) studied the effects of maleate on a neuromuscular preparation from 

 frogs, since he believed that maleate is a glycolytic inhibitor and, hence, 

 might interfere with the synthesis of acetylcholine. When maleate is applied 

 at 2.5 mM neuromuscular block definitely occurs before a depression of 

 the muscle. The block is established rather rapidly and it is doubtful if it 

 is in any way related to glycolytic inhibition. One recalls that work with 

 the mercurials may indicate SH groups on the acetylcholine receptors 

 (Turpaev, 1955; Nistratova and Turpaev, 1959), so the effects of maleate 

 on the response of the muscle to acetylcholine should be examined. Essen- 

 tially nothing is known about the actions of maleate on nerves, and it is 

 likely that penetration into axons must be limited. Yet Greengard and 

 Straub (1962) report that 0.15 mM maleate produces a small decrease 

 in the posttetanic hyperpolarization of sympathetic C fibers. From the 

 results on atria mentioned above, the neuromuscular block, and this ef- 

 fect on nerve fibers at a low concentration, it seems that a study of maleate 

 with respect to its actions directly on cell membranes might be interesting. 

 The observation of Lundegardh (1944) that maleate causes a rapid fall 

 in the membrane potential of wheat root cells is also evidence for a mem- 

 brane effect. 



Spermatozoal motility is depressed by maleate but not by fumarate. 

 Lipschitz and Hertwig (1921) found that frog spermatozoa are unaffected 



