ION MOVEMENTS DURING VAGUS INHIBITION OF THE HEART 115 



ability by chemical transmitters was soon applied to the inhibitory situation 

 in the heart, and in 1953 Burgen and Terroux put forward evidence for the 

 hypothesis that acetylcholine and related substances act on cardiac muscle 

 fibres by increasing their permeability to potassium ions (Burgen and Terroux, 

 1953). Against the background of the ionic theory of electrical activity in 

 nerve and muscle (Hodgkin, 1951) this hypothesis can account satisfactorily 

 for all the features observed during vagal stimulation or apphcation of acetyl- 

 choUne to auricular and pacemaker fibres (Hoffman and Suckfing, 1953; 

 West et al, 1956; del Castillo and Katz, 1957; Hutter and Trautwein, 1956) 

 and it received further support from measurements of membrane resistance 

 (Trautwein et al., 1956; Trautwein and Dudel, 1958). 



The aim of the work which is described in this article was to explore how 

 far radioactive isotopes may be usefully employed in the analysis of the 

 mechanism of synaptic inhibition and, if possible, to take advantage of the 

 inherent specificity of this technique to characterize more closely the perme- 

 ability change produced by acetylcholine in the heart. The experiments were 

 made in collaboration with Dr. E. J. Harris and the principal results have 

 already been reported briefly on previous occasions (Harris and Hutter, 1956; 

 Hutter, 1957; Harris, 1959). 



In the selection of a preparation we were influenced by the argument, 

 based on consideration of the situation at the neuromuscular junction, that 

 the permeability channels opened by chemical transmitters may exist in 

 parallel with channels that normally allow the passage of ions. It seemed 

 important therefore to choose a tissue much of whose surface is sensitive to 

 acetylcholine; for a locahzed increase in ion permeability might well be 

 swamped by the ionic fluxes which go on all the time through ordinary chan- 

 nels. From this point of view the sinus venosus of the frog or tortoise heart 

 seemed promising. Experiments with microelectrodes (Hutter and Trautwein, 

 1956) had shown that in the sinus venosus the effect of vagus stimulation is 

 often intense enough to render the tissue completely inexcitable and when 

 action potentials could be elicited by direct stimulation their height and 

 duration was found to be so greatly reduced throughout the tissue that a 

 considerable and widespread increase in the permeability to one or more of 

 the ions maintaining the resting potential was indicated. 



The sinus venosus also has another advantage for experiments with iso- 

 topes: it is so thin that all fibres have virtually free access to the medium. 

 Our estimate of the thickness of the frog's sinus venosus, from measurements 

 of weight and area is about 100 /z, though in the tortoise a muscular band 

 two or three times as thick may exist around the sinoauricular junction. A 

 less desirable property of the sinus venosus is that it contains a good deal of 

 connective tissue in close association with the cardiac muscle fibres. This is 

 reflected in a high proportion of sodium to potassium in the tissue and makes 

 it difficult to determine the ionic concentration in the cardiac muscle fibres. 



