CELLULAR ELECTROPHVSIOLOGV OF THE HEART 



253 



FIG- 8 



£ 



mV 



mA/cm 



"T 



56 mV 

 ♦ 



Ik = I1, £no = 56 mV^e, (reduced [Na\) 



mal [No"*"]^) 

 5~mSEC 



mSEC 



■1-L 



FIG. 8. Separation of ionic current at constant voltage into 

 its component parts. Uppermost record: time course of mem- 

 brane potential during current records shown below. Middle 

 records: two superposed current curves obtained with axon in 

 solutions with normal and with reduced concentrations of Na"*". 

 The upper trace, actually obtained by interpolation, could 

 have been obtained by reducing [Na^]o so that Sns = 56 + £r. 

 Since S = SNa, li, is presumed to be carried entirely by K* 

 ions and so li = Ik- The lower current (I,), obtained at normal 

 [Na"'']o, has an early component carried by Na"*" ions. If change 

 in [Na*]„ has not altered Ik, I,\b is the difference between the 

 two current records: Ins = Ii — Ii- The lowest tracing, with 

 separate time scale shows this difference. Temperature, 8.5°C. 

 [From Hodgkin (53).] 



FIG. 9. Effects of sudden changes in transmembrane po- 



pendent on S. Since three M molecules have to move 

 into position to form a Na'*" channel, the rise in g^a 

 following a sudden depolarization is S-shaped (figs. 

 9 and 13), i.e., third order kinetics. 



The kinetics of the H substance are the same as 

 those of the M substance except that the variation of 

 the forward and backward rate constants with 

 voltage is reversed — i.e., the reaction H ;;:± H' is far 

 to the left at Sr and depolarization increases the rate 

 of movement to H'. However, the rate constants 

 governing this reaction are slower than those govern- 

 ing M' :^ M, equilibrium for H taking several 

 milliseconds (fig. 11, arrows). The fraction of H 

 molecules in the proper position is called the amount 

 of activation of gNa. The amount of activation at Sr 

 is about 0.6. Maintained hyperpolarization increases 

 activation to i.o and maintained depolarization 

 decreases it to o (fig. 1 1). 



A sudden depolarization thus has two effects on 

 gNa- M molecules move rapidly into position and 

 establish Na+ channels at sites where H molecules 



mmho/cm' 



4 6 



TIME (mSEC) 



5k 



mmho/cm^ 



tential of a squid giant a.xon on sodium conductance (gNa) 

 and potassium conductance (gn). First and third curves, time 

 course of membrane potential changes; second and fourth, 

 gfja and gK as functions of time. In both cases the membrane 

 was suddenly depolarized by 56 mv at t = o. The depolariza- 

 tion either was maintained beyond the end of the sweep (solid 

 voltage line) or the membrane was abruptly repolarized 

 (dashed lines) at t = 0.7 msec in first curve and at t = 6.3 

 msec in third curve. The resulting changes in gNa and gK are 

 shown as solid lines for the maintained depolarizations and as 

 dashed lines for the early repolarizations. Note that both 

 gpja and gK increase along S-shaped curves when the mem- 

 brane is depolarized but decrease along exponential curves 

 when the membrane is repolarized. Temperature, 8.5°C. 

 [After Hodgkin (53).] 



have not yet moved out of position; therefore, gpja 

 rises rapidly. Even as M molecules are moving into 

 position, however, H molecules are moving out of 

 position, although at a much slower rate. Conse- 

 quently, gNa ri.ses to a peak as M molecules align 

 with H molecules and then falls over a period of 

 several milliseconds as H molecules move out of 

 position. If the membrane were suddenly repolarized 

 after inactivation was completed, there would be 

 little change in gNa since most of the H molecules 

 would be out of position and gNa would already be 

 near zero. Nevertheless, M molecules would start 

 moving rapidly out of position and H molecules 

 would begin moving slowly into position. Since, 

 however, the M molecules would not be in position, 

 the movement of H molecules into place (activation) 

 would not produce an appreciable increase in gNa- 

 As this activation proceeded the peak gxa subsequent 

 to a sudden depolarization would increase until, 

 after several milliseconds, the peak gxa vvould again 

 be normal. Clearly, a sudden depolarization im- 



