64 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



A ^15? 



Fig. 3. A. Diagram showing postulated movement of sodium 

 and potassium ions across the membrane during an impulse 

 advancing in the direction of arrow, and the resulting alteration 

 of charge on the membrane and its recovery. B. Potential 

 distribution of the impulse along a nerve or muscle fiber. 

 C. Resulting flow of electric current both in the external 

 medium and within the fiber. Note the reversal of membrane 

 potential during the spike. Figure 3/J is drawn so that the 

 impulse is at approximately the same position as in figure 3.4 

 and C. 



is treated very iulK in the following chapter by 

 Tasaki. 



After the events depicted in figures 2 and 3, the 

 ionic hypothesis would predict that a length of nerve 

 fiber would have gained a quantity of Na ions that 

 was at least adequate to displace the charge on its 

 capacitance so that there is the maximum change in 

 the membrane potential, and that there would also 

 have been an equivalent loss of K ions in the recharg- 

 ing process. The actually observed values have been 

 several times larger, which is to be expected because 

 the periods of Na entry and K emission overlap so that 

 much of the ionic influx cancels out as far as the 

 membrane potential is concerned. Thus the immediate 

 energy source for the propagation of the impulse 

 derives from the concentration batteries for Na and K 

 ions, and metabolic energy is only later required in 

 order to restore the ionic composition. However, the 

 ionic flux per impulse is so small relati\e to the ionic 

 composition of the fiber that, even in the alj.sence of a 

 restorative process, many thousands of impulses can 

 be propagated along large nerve fibers without 



significaniK changing the effectiveness of the con- 

 centration batteries. 



The ionic hypothesis can also explain satisfactorily 

 a great many other properties of nerve fibers [(cf. 

 Hodgkin (49); Hodgkin & Huxley C52)], for example 

 the subthreshold and threshold phenomena including 

 the all-or-nothing behavior, the refractory period fol- 

 lowing the impulse, the effects of anelectrotonus and 

 catelectrotonus, including accommodation, the effects 

 produced on the nerve impulse and the other re- 

 sponses by changing the Na or K concentrations, or 

 both, in the external medium and in the axoplasm 

 (54). This is such an immensely impressive per- 

 formance that the ionic hypothesis of the nerve fiber 

 must rank as one of the great conceptual achieve- 

 ments in biology. 



It is admitted that as yet the ionic hypothesis, in so 

 far as it has been formulated, does not give a com- 

 plete description of the behavior of the nerve mem- 

 brane. For example the nature of the specific changes 

 in Na and K conductance is not explained; the in- 

 tensity-time courses of changes are merely measured 

 and utilized in the explanations. The effect of external 

 calcium ions on these conductances also is not yet 

 understood. Again, nothing is known about the manner 

 in which metabolic energy is employed to drive 

 sodium and potassium ions across the membrane 

 against their electrochemical gradient. 



As would be expected, such a comprehensive and 

 precisely formulated hypothesis has been subjected to 

 much critical attack. However much of this criticism 

 has been based on imperfectly controlled experiments. 

 For example deviations from the predicted effects of 

 variations in the external potassium concentrations 

 on the resting membrane potential probably have 

 been largely due to secondary changes in the internal 

 potassium. In this context great significance attaches 

 to the recent experiments of Hodgkin & Horowicz 

 (51) on the membrane potential of isolated single 

 muscle fibers. Extracellular diffusion time is thus re- 

 duced to a minimum, so that a steady membrane 

 potential is observed within a second of changing the 

 external ionic composition and thu« before there is any 

 appreciable change in the internal composition. 

 Under such conditions, with changes in (Kq), the ob- 

 served membrane potentials agree very closely with 

 those predicted by the ionic hypothesis. It was also 

 remarkable that, making use of the anomalous 

 rectification in K ionic diffusion across the membrane 

 [cf. Katz (59)], it was possible by changing the internal 

 composition of the muscle fiber to have a membrane 



