INHIBITION IN MOLLUSCAN HEARTS 137 



in auricle and ventricle of Mure.x tnuuuhis. Suzuki (1935) failed, however, to 

 find nerve cells in the heart of Lutraria maxima. Motley (1932) could not 

 detect ganglion cells in the heart of eight species of fresh-water mussels, and 

 Prosser (1940) reported that there are no nerve cells in the heart of Venus 

 mercenaria. 



The concepts of myogenic and neurogenic origin of the heartbeat are, of 

 course, not mutually exclusive as is demonstrated in the classical case of the 

 Linmlus heart where a nervous pacemaker dominates a muscular pacemaker, 

 which becomes evident only when the heart ganglion is removed. The pre- 

 sence of ganglion cells in certain hearts poses, however, an interesting prob- 

 lem with regard to the site of action of the extrinsic cardiac nerves. In gangli- 

 onated hearts these nerves may well exert their action through the mediation 

 of the ganglion cells of the heart, while in the absence of intracardiac nerve 

 cells the extrinsic nerves may make direct contact with the heart muscle 

 fibers. This question assumes particular importance with regard to the 

 problem of the chemical mediators involved in the regulation of the heart- 

 beat. 



In 1940 Prosser demonstrated that an isolated heart of Vemts mercenaria 

 is inhibited by the perfusion fluid from another Venus heart that has been 

 inhibited by stimulation of the visceral ganglion. The isolated heart of Venus 

 mercenaria was found to be inhibited by extremely small amounts of acetyl- 

 choline (10 11 g/ml) (Prosser, 1940; Welsh and Taub, 1948). For this reason 

 the Venus heart as well as the heart of many other lamellibranchs are employed 

 as test objects in bioassays for acetylcholine. Welsh and Taub (1948) have 

 studied the action of a large number of modifications of the acetylcholine 

 molecule. Their paper provides excellent evidence for the structure-activity 

 relationship of pharmacological agents. The results imply an interaction of 

 transmitter substance with specific receptor molecules, and a relationship 

 between transmitter and receptor that is comparable to the relationship 

 between substrate and enzyme. Their scheme was extended to include acetyl- 

 choline-blocking agents and indicated competitive inhibition of transmitter- 

 receptor interaction. As so often in pharmacological work the elegant picture 

 was somewhat spoiled by the finding that benzoquinonium chloride (Myto- 

 lon) was by far the most powerful blocking agent. Its structure has no re- 

 semblance to that of acetylcholine. 



It is now known that the hearts of a great number of molluscs belonging 

 to the gastropods, lamellibranchs and the cephalopods are inhibited by acetyl- 

 choline and that they are accelerated by 5-hydroxytryptamine (5HT) (see the 

 reviews of Krijgsman and Divaris, 1955; Welsh, 1957). For the heart of 

 Venus mercenaria it is reasonably well established that acetylcholine is the 

 transmitter substance of the cardio-inhibitory fibers: during nervous in- 

 hibition a substance is released which has the same effect on the heart as 

 acetylcholine; eserine prolongs the inhibition resulting from stimulation of 



