12.3. The full Hodgkin–Huxley mechanism and its molecular underpinnings[[Student version, January 17, 2003]] 469
Figure 12.13:(Oscilloscope traces.) Perhaps the most remarkable experiment described in this book. (a)Action
potential recorded with an internal electrode from an axon whose internal contents have been replaced by potassium
sulfate solution. (b)Action potential of an intact axon, with same amplification and time scale. [From Baker et al.,
1962.]
then used these measurements to explain the action potential. Though they suspected that their
membrane conductances arose by the passage of ions through discrete, modularion channels,
nevertheless their data could not confirm this picture. Indeed, the discussion of this chapter so far
leaves us with several questions:
a.What is the molecular mechanism by which ions pass through a membrane? The simple
scheme of diffusion through the lipid bilayer cannot be the answer (see Section 4.6.1 on page
121), because the conductance of pure bilayer membranes is several orders of magnitude less
than the value for natural membranes (see Section 11.2.2).
b.What gives this mechanism its specificity for ion types? We have seen that the squid axon
membrane’s conductances to potassium and to sodium are quite different and are gated dif-
ferently.
c.How do ion channels sense and react to the membrane potential?
d.How do the characteristic time courses of each conductance arise?This subsection will briefly sketch the answers to these questions, as discovered starting in the
1970s.
Hodgkin and Huxley could not see the molecular mechanisms for ion transport across the axon
membrane because they were observing the collective behavior of thousands ion channels, not the
behavior of any individual channel. The situation was somewhat like that of statistical physics at
the turn of the twentieth century: The ideal gas law made it easy to measure the productNmolekB,
but the individual values ofNmoleandkBremained in doubt until Einstein’s analysis of Brownian
motion (Chapter 4). Similarly, measurements ofgiin the 1940s gave only the product of the
conductanceGiof an individual channel times the number of channels per unit area of membrane.
Katz succeeded in the early 1970s in estimating the magnitude ofGibyanalyzing the statistical
properties of aggregate conductances. But others’ (inaccurate) estimates disagreed with his, and
confusion ensued.
The systematic study of membrane conductance at the single-channel level had to await the
discovery of cell-biological techniques capable of isolating individual ion channels, and electronic