CELLULAR ELECTROPHYSIOLOGY OF THE HEART 



257 



120t ^Nq"^'- I ^IG- 15 



FIG. 14. Calculated (above) and measured (below) mem- 

 brane action potentials of squid giant axon. Number next to 

 each curve is the amount of charge in nanocoulombs/cm^, 

 displaced from the membrane by the brief stimulating current 

 applied via long internal and external electrodes. Since mem- 

 brane capacity was taken as i.o ;uF/cm- in the calculations, the 

 number by each theoretical curve also indicates the initial 

 millivoltage displacement. The upper curves are solutions of 

 equation 12. Ordinate: displacement of transmembrane po- 

 tential from the resting level, depolarization upward. Abscissa : 

 time in milliseconds. The two sets of curves are directly com- 

 parable except for the slight curvature of the i 10 mv calibra- 

 tion line. Calculations for a temperature of S^C. [After Hodgkin 

 & Huxley (60).] 



TIME (mSEC) 



FIG. 15. Theoretical propagated action potential. Plots of 

 transmembrane potential alteration (£ — f,), potassium 

 conductance (gx), and sodium conductance (gN,, I as functions 

 of time at a fixed point on a squid axon during the passage of a 

 propagated action potential. Curves are solutions of equation 

 12 but with Im replaced by —{i/TyU^jd'H/dx?, where u is 

 conduction velocity, 18.8 m/sec and r, is internal resistance 

 in ohm /cm. The horizontal lines labeled (£n.i — Sr) and (Sk — 

 £r) represent the Na"*^ and K+ equilibrium potentials, respec- 

 tively. Note that gjj„ does not change appreciably until the 

 time of the rising phase inflection point of the action potential, 

 and that £ approaches £k during the after potential when g^ 

 is still elevated. Calculated for a temperature of i8.5°C. [After 

 Hodgkin (53).] 



changes of Na+ and K+ during activity; r) the exist- 

 ence of a propagating action potential having constant 

 velocity and amplitude (fig. 15) and that membrane 

 resistance falls dramatically during passage of the 

 action potential (18); and/) cathodal or depolariza- 

 tion block of conduction. This behavior is inherent in 

 the kinetics of the gNa activation-inactivation process, 

 i.e., depolarization inactivates. 



that threshold £ becomes more negative. Thus the fall 

 in S upon termination of the current will cause an 

 increase in gNa while gK remains at its low value for 

 a period and a regenerative response may occur. Since 

 the resting value of h is only 0.6 (fig. 1 2), hyperpolari- 

 zation could almost double the available gNa- Thus, 

 anodal break excitation is a possibility in any excita- 

 ble tissue if h at Sr is appreciably less than i . 



THRESHOLD AND ANODAL BREAK EXCITATION. It Can be 



seen in figure 14 that the threshold of the theoretical 

 action potential measured at the voltage minimum is 

 about 6 mv. The corresponding minimum value for 

 the nerve is about 8 mv. This agreement is more or 

 less fortuitous, since the threshold is quite sensitive to 

 the value of gi, which is not accurately known. How- 

 ever, the theoretical model closely resembles the nerve 

 in this respect. The equation can also predict anodal 

 break excitation, i.e., the initiation of an action poten- 

 tial as a result of the sudden cessation of a hyperpolar- 

 izing current. Prolonged hyperpolarization has two 

 effects: gx decreases and h increases (activation) so 



IONIC EXCHANGE. Since the net Na"*" and K"*" currents 

 are known at each instant, the one-way flux can be 

 calculated if it is assumed that each ion moves through 

 the membrane independently of any other ion. The 

 net fluxes calculated in this way agree fairly well with 

 the measured fluxes (83), but too little exchange of 

 Na+ and too much exchange of K+ are predicted. 

 Although a portion of the error may result from recog- 

 nized simplifications in the formulation, the assump- 

 tion of independent movement is now known to be 

 incorrect for K+ (65). Furthermore, the connective 

 tissue sheath siuTounding the squid membrane acts as 

 a diffusion barrier to K+ (44). 



