EFFECTS ON TISSUE FUNCTIONS 361 



must contribute to some extent. The results were discussed in terms of 

 the role of SH groups in the axonal membrane structure and the generation 

 of the action potential. 



The injection of 0.5 mg of iV-ethylmaleimide into the carotid artery 

 brings about marked changes in the transmission across the cat cervical 

 sympathetic ganglion (Komalahiranya and Voile, 1963). The effects are 

 divided chronologically into 3 phases: 



Phase I (0-10 min): The amplitude of the postganglionic action potential 

 is somewhat increased but postganglionic firing induced by injections of 

 acetylcholine or K+ is completely blocked. Denervated ganglia treated 

 with xV-ethylmaleimide also lose their response to acetylcholine and K+. 



Phase II (10-45 min): The postganglionic response to preganglionic 

 stimulation is reduced and occasionally blocked irreversibly. At this time 

 the postganglionic responses to acetylcholine and K+ are markedly en- 

 hanced. Retrograde firing induced by K+ is also enhanced. 



Phase III (45-120 min): Spontaneous asynchronous discharges occur 

 in both pre- and postganglionic nerves and this is not prevented by the 

 usual ganglionic blockers. 



The initial enhancement of the postganglionic spike they attribute to a 

 preganglionic site of action, possibly an increase in the release of acetyl- 

 choline, and the transmission block later to a postganglionic action, which 

 is nonspecific since it applies to both acetylcholine and K+. The early and 

 late phases are similar to the effects of high and low Ca++, respectively, 

 and it is suggested that iV-ethylmaleimide may disturb Ca++ balance in 

 some way, possibly initially releasing Ca++ from extraneural sites and 

 thereby increasing Ca++ concentration in the ganglion, and eventually 

 depleting Ca++ from the ganglion itself. They also point out that choline 

 acetylase is an SH enzyme and might be inhibited by iV-ethylmaleimide, 

 this contributing to the block by reducing the synthesis of acetylcholine. 



Erythrocyte Permeability, Active Transport, and Hemolysis 



The effects of the mercurials and ^V-ethylmaleimide on erythrocytes are 

 quite different. Whereas p-MB readily produces hemolysis in a predictable 

 manner, V-ethylmaleimide does not; indeed, no hemolysis of human 

 erythrocytes occurs after 5 hr in 0.5 vcvM iV'-ethylmaleimide (Sheets et al., 

 1956 b). The respiration of erythrocytes is inhibited 50% by 1.3 mM and 

 completely by 2.6 mM A'-ethylmaleimide, so this inhibitor can affect 

 metabolism without disrupting the membrane structure, which p-MB 

 cannot do (Sheets and Hamilton, 1958). Furthermore, iV-ethylmaleimide 

 is much more effective than p-MB in reducing erythrocyte glutathione 



