456 Chapter 12. Nerve impulses[[Student version, January 17, 2003]]
The following subsections will explore a simplified, one-shot model for the action potential,
starting with some more details about membrane excitability. Section 12.3 will return to the puzzle
of how real action potentials can be self-limiting.
12.2.2 Just a little more history
After showing that living cells can maintain resting potentials, DuBois Reymond also undertook a
systematic study of nerve impulses, showing around 1866 that they traveled along the axon at a
constant speed. The physical origins of this behavior remained completely obscure.
It seemed natural to suppose that some process in the cell’s interior was responsible for carrying
nerve impulses. Thus for example when it became possible to see microtubules running in parallel
rows down the length of the axon, most physiologists assumed that they were involved in the
transmission. In 1902, however, Julius Bernstein set in motion a train of thought that ultimately
overturned this expectation, locating the mechanism of the impulse in the cell’s plasma membrane.
Bernstein correctly guessed that the resting membrane was selectively permeable to potassium.
The discussion in Section 11.1 then implies that a cell’s membrane potential should be around
− 75 mV,roughly as observed. Bernstein suggested that during a nerve impulse the membrane
temporarily becomes highly permeable toallions, bringing it rapidly to a new equilibrium with
no potential difference across the membrane. Bernstein’s hypothesis explained the existence of a
resting potential, its sign and approximate magnitude, and the observed fact that increasing the
exterior potassium concentration changes the resting potential to a value closer to zero. It also
explained roughly the depolarization observed during a nerve impulse.
Hodgkin was an early convert to the membrane-based picture of the action potential. He
reasoned that if the passage of ions through the membrane was important to the mechanism (and
not just a side-effect), then changing the electrical properties of the exterior fluid should affect the
propagationspeedof the action potential. And indeed, Hodgkin found in 1938 that increasing the
exterior resistivity gave slower-traveling impulses, while decreasing it (by laying a good conductor
alongside the axon) almost doubled the speed.
Detailed tests of Bernstein’s hypothesis had to await the technological advances made possible
byelectronics, which were needed in order to measure signals with the required speed and sensi-
tivity. Finally, in 1938 K. Cole and H. Curtis succeeded in showing experimentally that the overall
membrane conductance in a living cell indeed increased dramatically during a nerve impulse, as
Bernstein had proposed. Hodgkin and Huxley, and independently Curtis and Cole, also managed
to measure ∆V directly during an impulse, by threading a tiny glass capillary electrode into an
axon. Each group found to their surprise that instead of driving to zero as Bernstein had proposed,
the membrane potential temporarily reversed sign,as shown in Figure 12.6b. It seemed impossible
to reconcile these observations with Bernstein’s attractive idea.
Further examination of data like Figure 12.6b revealed a curious fact: The peak potential (about
+42mVin the figure), while far from the potassium Nernst potential, is actually not far from the
sodiumNernst potential (Table 11.1 on page 416). This observation offered an intriguing way to
save Bernstein’s selective-permeability idea:
If the membrane could rapidly switch from being selectively permeable to potas-
sium only, to being permable mainly to sodium, then the membrane potential
would flip from the Nernst potential of potassium to that of sodium, explaining
the observed polarization reversal (see Equation 12.3).