FIG. 26. Effects of vagal stimulation on the transmembrane 

 potential of a pacemaker cell in the frog sinus venosus. Period 

 of vagal stimulation at 20/sec is indicated by interruption in 

 lower white line. Only the lower part of the action potential 

 is shown , total visible voltage excursion is about 45 m\-. [From 

 Hutter & Trautwein (76).] 



potential is a positive after-potential. Tlie.se action 

 potentials have a sharp threshold for repolarization. 



EFFECTS OF V.^GAL AND SVMP.^THETIC STIMULATION. 



Although the heart is spontaneously active, its rate 

 is almost pre-emptorily controlled by vagal and 

 sympathetic discharges in the sinoatrial pacemaker 

 region. The mode of action of the vagal transmitter 

 acetylcholine (AC^h) is well vmderstood. The action 

 of epinephrine is uncertain since the evidence is 

 conflicting (cf. 72). Figure 26 shows the effects of 

 vagal stimulation on the transmembrane potentials 

 of a frog sinus venosus fiber. Rapid vagal stimulation 

 caused immediate hyperpolarization and stoppage 

 of impulse generation (11, 76). The action persisted 

 for the duration of the stimulation. Following cessa- 

 tion of the stimulation, the potential fell gradually 

 and impulse discharge resumed at an initially slower 

 rate. Slower \agal ner\e stimulation ma\- slow the 

 heart rate. 



Since Sn., and Sci are both more positive than the 

 large negative voltage reached during vagal inhibi- 

 tion, the transmitter must act to increase gK or to 

 decrease gci, and/or gxa. There is considerable 

 evidence that membrane conductance is greatly 

 increased by vagal stimulation (122) and ACh (119, 

 120) so an increase in gK is the probable effect of the 

 transmitter. An increase in gn produces a powerful 

 inhibition since it tends to clamp the voltage at Sk- 

 Hutter and Harris have shown directly that ACh 

 acts specifically to increase gK [see (72) and Hutter 

 in (41)]. ACh increased both the efflux and the influx 

 of K+ [see also (loi)]. Figure 27 shows the dramatic 

 effects of ACh on K""- efflux from tortoise sinus veno- 

 sus. Cl~ fluxes were not appreciably affected. Evi- 

 dence leading to this conclusion was furnished earlier 

 by Trautwein & Dudel (119). They found that the 



CELLULAR ELECTROPHYSIOLOGY OF THE HEART 277 



5 X 10' r 



\ 



E5 





2x 10 



Ix 10 



MIN 



FIG. 27. Effect of vagal stimulation on the efflu.x of K''^ 

 from quiescent tortoise sinus venosus. The total radioactivity 

 of the tissue is shown by the dots and the logarithmic ordinate 

 scale at left. The rate constant of K"*" release by the tissue is 

 shown by the bar graph and the linear scale at the 

 right (min^'). Abscissa: time in min. The vagus nerve was 

 stimulated (lo/sec) during the period subtended by the 

 bracket (52-59 min). Note the quadrupling in the rate con- 

 stant due to the stimulation. This effect is also shown by the 

 increased negative slope of the tissue radioactivity curve. 

 [After Hutter, in (41).] 



equilibrium potential for ACh inhibition varied 

 exactly as Sk with variations in [K+Jo and this value 

 of Sk agrees with the 8k calculated from G and 8 

 during diastole (37). Woodbury and Crill (in 41) 

 furnished less direct evidence in that the decrease in 

 membrane resistance produced by ACh was not 

 affected by Cl~ replacement, although CI"" replace- 

 ment in the absence of ACh caused an increase of 

 25 per cent or more in membrane resistance. Hoffman 

 & Suckling (70) found that ACh dramatically shortens 

 the atrial action potential. Action potentials elicited 

 by direct stimulation during vagal stimulation have 

 less overshoot and shorter durations than normal, 

 as would be expected from an increase in gK. The 

 effects of ACh on heart tissue are somewhat different 

 from its effects at neuromuscular junctions, where 

 it produces an increase in membrane permeability 

 to "all" ions. The differences may be reconciled if it 

 is supposed that ACh increases membrane permeabil- 

 ity by creating pores which are slightly larger in end- 

 plate membranes than in cardiac muscle membranes. 

 The effects of sympathetic stimulation on the ac- 

 tion potentials of a frog sinus venosus cell are shown 

 in figure 28 (76). In this tissue, such stimulation in- 

 creases the rate of discharge and the overshoot of 

 the action potential. Hutter & Trautwein (76) also 

 observed an increased rate of rise of the action po- 

 tential during .sympathetic stimulation. 



