CELLULAR ELECTROPHVSIOLOGY OF THE HEART 275 



described here have one or more serious defects. 

 Further experimentation is needed to determine the 

 process of repolarization in terms of the kinetics of 

 the changes in membrane ionic conductances or 

 permeabiUties. Until voltage-clamping in cardiac 

 cells becomes technically feasible, the most fruitful 

 experimental approach seems to be to study how 

 applied currents of different strengths, currents 

 applied at different initial S's and external ion con- 

 centrations affect 8. 



Despite the lack of an adequate hypothesis of 

 repolarization, several positive statements can be 

 made about this process, a) Repolarization consists 

 of the slow movement of a stable equilibrium point 

 with £ pursuing it. b) The increased S of the third 

 phase is due to an increase in g,.q, not to a sudden 

 jump in the position of S,., occasioned by the dis- 

 appearance of one stable and one unstable point. 

 c) The slope of the Ii,£ curve is positive for all voltages 

 of the normal action potential at all times during 

 repolarization (fig. 21). d) Reduced [Ca++]o appar- 

 ently changes the instantaneous Ii,S curves so that 

 they have a region of negative G in the vicinity of 

 £ = o. These statements lead to the conclusion that 

 the conductance changes of repolarization in heart 

 result from rate processes which are largely time- 

 dependent and only slightly voltage-dependent. If 

 this conclusion is correct, then repolarization in heart 

 is an entirely different process than in squid axon 

 and considerably more experimental data are re- 

 quired to elucidate the kinetics of this relatively un- 

 known process in heart. Any successful hypothesis 

 must give an ionic basis for this behavior as well as 

 explain superimposability and variation of Iap with 

 stimulus interval. 



Auto-rlivthmicity 



Perhaps the most striking property of cardiac 

 muscle is its spontaneous contractions. Since the 

 contractile state is controlled by the transmembrane 

 potential, rhythmic contraction is a consequence of 

 rhythmic initiation of impulses. It is commonly be- 

 lieved that all cardiac cells are intrinsically rhythmic. 

 In the intact heart the beat originates in a histologi- 

 cally specialized region, the sinoatrial node, because 

 its intrinsic rate is the highest. Regardless of its 

 anatomical location, the site of origin of the beat 

 is called the pacemaker region. The distinguish- 

 ing electrical characteristic of a pacemaker cell is 

 lack of a stable equilibrium voltage — rapid repolari- 

 zation being immediately succeeded by a slow diastolic 



FIG. 25. Transmembrane action potentials from the sinus 

 venosus and atrium of a frog. Ordinates: transmembrane 

 potential in millivolts. Abscissae: time; dots are 0.2 sec apart. 

 A: microelectrode recording from a pacemaker cell. Note the 

 large diastolic depolarization and the comparatively gradual 

 transition to the upstroke of the action potential. B: recording 

 from a cell a short distance away. C: recording from atrial 

 cell. Rate of all three cells is determined by the time required 

 for the slow depolarization shown in .-1 to reach threshold. 

 [From Hutter &; Trautwein (76).] 



depolarization called the prepotential (2) or pace- 

 maker potential. This depolarization contrasts to 

 the unx'arying diastolic potential of other cardiac 

 cells. Figure 25 sliovvs a .series of intracellularly re- 

 corded tran.smembrane action potentials from the 

 sinus venosus and atrium of frog (76). The potential 

 in figure 25.-! is from a pacemaker cell. There is a 

 comparatively gradual transition between the slow 

 diastolic depolarization and the rapid upstroke of 

 the action potential. In B, the microelectrode was in a 

 fiber a short distance away, where there were a smaller 

 diastolic depolarization and a more abrupt transition 

 to the rising phase of the action potential. Simul- 

 taneous recordings from these two regions (2, 12) 

 show that activity of the type shown in figure 25 

 occurs earliest; therefore, impulses are initiated in 

 this region. Figure 25C is a recording from an atrial 

 fiber in which £ is constant during diastole. The 

 records of figure 25 illustrate the transition from pace- 

 maker to ordinary cardiac tissue. Presumably, re- 



