448 The Molecular Basis of Nerve Conduction /24 : 4 



potential changes of the membrane with time. The results of a series of 

 experiments showed that when a negative current was applied, that is, 

 the membrane potential was increased in the direction of the resting 

 potential, the membrane potential changed rapidly, and then fell 

 slowly to its equilibrium value. If this were a passive element, it should 

 have returned to zero at the end of the 8 /xsec surge to charge the 

 capacity; instead, it was still appreciably different at the end of 1 msec, 

 or 1,000 /usee! 



The results were very different when pulses were used to depolarize 

 the membrane. If the depolarization was sufficiently weak, the curve 

 shape was similar to that obtained with increased polarization. At a 

 sharp threshold around 18 nui coulombs/cm 2 , a dramatically different 

 type of response occurred resembling a spike potential. In this case, 

 the membrane potential changed to a different equilibrium value deter- 

 mined by the membrane, the change occurring more rapidly the greater 

 the stimulus. 



These experiments showed the membrane was not passive. The 

 experiments also revealed that comparatively long sections of the 

 membrane could be excited to produce a potential whose time course 

 resembled a transmitted spike potential. The current-voltage curves 

 were difficult to interpret unless some physical parameter was held 

 constant. 



In order to hold the potential across the membrane constant, an 

 electronic feedback circuit was used. A simplified form is presented in 

 Figure 6. The membrane potential is measured essentially between 

 electrodes b and c. This is applied to a high-input impedance amplifier, 

 so that no current will flow and the electrodes will not become polarized. 

 A predetermined voltage V is then subtracted from V. The difference 

 is amplified and fed to the current generator in such a fashion that 

 V — V is reduced to zero. The current flowing through the membrane 

 is measured in terms of the potential difference between electrodes c and 

 d, plus a knowledge of the resistance of the external medium used. 

 These electrodes are also applied to a high-input impedance amplifier 

 to avoid polarization. The amplified current is indicated on the 

 graphic recorder. This circuit supplies the necessary current so that 

 the membrane potential will remain clamped at V = V Q , no matter 

 how the membrane impedance may change with time. The clamped 

 voltage can be easily and rapidly changed by the experimenter. Records 

 obtained are presented in Figures 7 and 8. 



One phenomenon illustrated by these curves is the smallness of 

 currents obtained for increased polarization, compared to those obtained 

 for decreased polarization. Another is that of both effects having a 

 marked time dependence. Most remarkable is that above a certain 



