26o 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



electrode. The variation of Sd with [Na+]o would be 

 expected from the ionic theory, since gNa would be 

 much larger than gK + gci early in depolarization. 

 Draper and Weidmann also found that the tissue be- 

 came ine.xcitable when [Na+]o was less than about 

 15 per cent of normal. 



This indirect evidence indicates that depolarization 

 in cardiac tissue results from a net influx of Na+. 

 However, some doubt was thrown on this conclusion 

 by Coraboeuf & Otsuka's (2 1 ) finding that overshoot 

 in guinea pig ventricle was independent of [Na+]o 

 except that the tissue became inexcitable at low 

 [Na+]o values. DeLeze (31) confirmed these results, 

 but he also found that Sd does depend directly on 

 [Na+]o. 



Working with frog ventricle, Brady & Woodbury 

 (4) found that overshoot varies with 8xa when [Na+]o 

 is greater than 40 per cent of normal. There is, 

 however, comparatively little change in overshoot if 

 [Na+]o is less than 50 per cent. Figure i6^4 shows 

 superimposed traces of frog ventricular action poten- 

 tials obtained for various values of [Na+]o; choline+ 

 replaced Na+. Note the near equality of overshoot in 

 the solutions in which [Na+]o was 40 and 50 per cent 

 of normal. Brady and Woodbury also observed an Sd 

 directly proportional to [Na+]o. Although the abso- 

 lute values of Sd varied considerably from one cell to 

 the next, the variation with [Na+]o was convincing in 

 a single impalement (fig. 16B). The regression line 

 relating all values of Sd to [Na+]o passed through zero, 

 if allowance was made for experimental error (fig. 

 16C). Thus the evidence concerning effects of [Na+]o 

 on Sd indicates that Na+ is the depolarizing agent. On 

 the other hand, the effects of [Na+]n on overshoot are 

 equivocal. 



In the squid giant a.xon, gx^ is falling and gx is 

 beginning to rise at the peak of the action potential 

 (fig. 15). The time when gNa/gK is maximum is 

 earlier than this — probably immediately after the in- 

 flection point. Thus, if the ionic theory is applicable 

 to heart, nearly all membrane current is carried by 

 Na+ during the early rising phase. In this case, the 

 rate of rise is proportional to Ins, since — CmSd = 

 li di Ins = gNa(S — Sn„). So, if the voltage of the 

 inflection point and gNM are independent of [Na+]o, 

 Sd should vary with S^a. It is likely that gNa varies 

 directly with [Na+]„ also. Other ions must be con- 

 tributing significantly at the peak since it is con- 

 siderably below Sn,,. Thus, the failure of variations 

 in [Na+]o to change overshoot cannot rule out the 

 high probability that Na+ is the depolarizing agent 

 [see (4) for further discussion]. Since Na"*" carries 



(mV) 



0- 



-50 



-100 



(^ 



110% //voV, 



100- ^ 



[No''"] % of normal 

 "• ■'o 



FIG. 16. Effects of changes in [Na+]o on the transmembrane 

 potentials recorded from cells of perfused frog ventricle. 

 A: effects of [Na+]o on overshoot and repolarization. Numbers 

 by curves indicate percentage of normal [Na*]o in perfusion 

 fluid; choline substituted for Na*. Ordinate: transmembrane 

 potential in millivolts; abscissa : time in seconds. [After Brady & 

 Woodbury (3).] B: effects of [Na"'"]o on rising phase of action 

 potential (£ — £r), on the left and rate of rise (S, v/sec), on 

 the right recorded from single cell. Lowering [Na+Jo (by 

 substituting sucrose for NaCl) reduced overshoot and rate of 

 rise. C: effects of [Na+]„ on the maximum rate of depolariza- 

 tion (Sd) for a large number of cells (NaCl replaced by su- 

 crose). The line is a least square fit of the data and the ver- 

 tical axis intercept is not significantly different from zero. 

 [After Brady & Woodbury (4).] 



nearly all the depolarizing current, peak g^., r^ 

 — C„iSd/ (S — Sno)- Accepting the rather high \alue 

 of 30 fiF/cm- for the C, of cardiac tissue (122), Brady 

 & Woodbury (4) estimated a peak gxa of 10 

 mmho cm'-. Hodgkin & Huxley (60) found a maxi- 

 mum gNa of about 25 mmho 'cm- in squid axon and 

 Cole & Moore (19) have reported values up to 140 

 mmho/cm'-. A similar calculation of gNa based on 

 data from Purkinje fibers (126, 127) gives a peak 

 value for gN„ of about 100 mmho/cm-, although 

 there is consideral)le uncertaint\' in the \alues of 



