CELLULAR ELECTROPHYSIOLOGY OF THE HEART 



25' 



mv in the low Na+ and io8 mv in the high Na+ 

 solutions. However, if the records of Ii obtained 

 at these depolarizations are compared, they closely 

 resemble each other. After a correction for the change 

 in resting potential produced by altering [.\a+]o, the 

 change in the voltage at which the initial current is 

 zero is within i mv of the change in S.va calculated 

 from the Nernst equation. This is an extremely good 

 agreement between measured and calculated v'alues 

 in a biological system and strong e\'idence that the 

 initial current is carried b\' Xa+. Although [Na+]i was 

 not estimated in these fibers, Sx,, calculated from 

 measurements of [Na+]i in other fibers in similar 

 condition was 45 to 50 mv, a value close to the zero 

 initial current voltage. 



Just as the initial inward Na+ current has the 

 proper direction to produce the rising phase of the 

 action potential, the delayed rise in outward current 

 has the proper direction and time course to produce 

 the rapid repolarization of the falling phase in a squid 

 giant axon. Since this outward current is still present 

 in Cl~ deficient solutions (53), it seems likely that the 

 prolonged outward current is carried by K"*'. It is 

 difficult to obtain direct evidence to this efTect because 

 an outward current should be little aflfected by 

 changes in external concentrations of cations. There is, 

 however, convincing tracer and other e\idence that 

 the prolonged high density outward membrane cur- 

 rents of depolarization are carried by K+ (61). It will 

 be assumed, henceforth, that this current is carried by 

 K+. Figure 7 shows a plot of 1 1 as a function of clamp 

 voltage, Ii being measured at short times (Ino) and 

 long times (Ir)- The significance of these curves will 

 be discussed in the section on repolarization in cardiac 

 tissue. 



SEPARATION OF SODIUM AND POTASSIUM CURRENTS. In 



principle, the K"^ moiety of the total membrane cur- 

 rent at a particular constant voltage (So) can be ob- 

 tained directly by changing the [Xa+]„ until S^a = 

 £0 and iNa = o. In practice it would be difficult to 

 change Sno by exactly the desired amount and to 

 repeat this procedure for each £0. Hodgkin & Huxley 

 (57) separated Na+ and K+ currents by interpolating 

 between current records at different voltages and 

 [Na+]o's to get I i at £ = £x..,. Figure 8 shows the 

 separation of Ii into Ixa + Ik> 'o'" a depolarization of 

 56 mv. Curve Ii was obtained for a normal [Na+Jo = 

 460 mmoles per liter. Here Ii = Ik + iNa- Curve Ii 

 was interpolated from records obtained in low 

 [Na+]o solutions and is the current that would have 

 been recorded with [Na+]o reduced to a value such 



Ii 

 mA/cm 



100 +150 



FIG. 7. Current, potential curves for short and long times 

 after sudden changes in membrane potential of the voltage- 

 clamped squid axon. Ordinate; membrane ionic current 

 density, I, (m.^/cm-), measured 0.63 msec after change in 

 potential (open circles) and steady current measured 12 to 

 40 msec after change in potential (solid circles). .\n outward 

 current is positive. Abscissa ; difference between the clamp 

 potential and the resting potential, £ — £r (mv); depolariza- 

 tion is to the right. The curve for long times has a positive 

 slope at all £'s; whereas the curve for t = 0.63 msec has a 

 positive slope for £ — S r less than about 5 mv and greater than 

 about 70 mv and a negative slope from 5 to 70 mv. The short 

 time curve thus has the "N" shape often referred to as a 

 "dynatron" characteristic. Currents are much larger for 

 depolarizations than for hyperpolarizations. Temperature, 

 3.8°C. [After Hodgkin et at. (62).] 



that fixa = 56 + £r- Since Ixa = o at £ = £xa, mem- 

 brane ionic current is carried by K+; Ii = Ik- Fur- 

 thermore, the difference between Ii and Ii for a 

 depolarization of 56 mv is the Na+ current: Ixa = 

 Ii — Ii (lowest curve, fig. 8). Similar separations are 

 possible for all clamp voltages. The separated curves, 

 like the total current curves, are continuous in time 

 at a constant voltage (figs. 5 and 6) and continuous in 

 voltage at a fixed time (fig. 7). It can be seen that l^^ 

 reaches a peak then gradually falls to a value near 

 zero even though the membrane is kept depolarized. 

 This decline of Ixa in time was termed "inactivation" 

 by Hodgkin & Huxley (59). 



SODIUM AND POTASSIUM CONDUCTANCES (58). Both the 



inward and the outward membrane current under 

 voltage clamp are carried by ions moving down their 

 electrochemical gradients. The current carried by one 

 ion species is determined by both the ease with which 

 the ions can penetrate the membrane (permeability) 

 and the driving force on the ion (electrochemical 

 gradient). Since the objective is to characterize mem- 

 brane properties and since the average driving force 

 is known, a fairly direct measure of these membrane 

 properties can be obtained by dividing the ionic 



