Biological Physics: Energy, Information, Life

472 Chapter 12. Nerve impulses[[Student version, January 17, 2003]]

in

out

a

resting

state with

closed

active Na+

channel

initial

depolarization

<0.1ms

inner

vestibule

channel-inactivating segment

gate

sensing

alpha

helix

movement of

α helix and

opening

of channel

Na+

Na+

b

Figure 12.16:(Schematic; sketch.) (a)Conceptual model of a voltage-gated ion channel. A spring normally holds
avalve closed. An electric field pointing upward lifts the positively charged valve, letting water flow downward.
(b)Sketch of the sodium channel.Left:In the resting state, positive charges in the channel protein’s four “sensing”
alpha helices are pulled downward, toward the negative cell interior. The sensing helices in turn pull the channel into
its closed conformation.Right:Upon depolarization, the sensing helices are pulled upward. The channel now relaxes
toward a new equilibrium, in which it spends most of its time in the open state. The lower blob depicts schematically
the channel-inactivating segment. This attached object can move into the channel, blocking ion passage even though
the chanel itself is in its open conformation. [After Armstrong & Hille, 1998.]

barrier. (In addition, sodium holds its hydration shell more tightly than does potassium, due to its
smaller size.)

c. Voltage-gating Already in 1952, Hodgkin and Huxley were imagining voltage-gated channels
as devices similar to the fanciful valve sketched in Figure 12.16a: A net positive charge embedded in
amovable part of the channel gets pulled by an external field. An allosteric coupling then converts
this motion into a major conformational change, which opens a gate. Panel (b) of the figure shows
amore realistic sketch of this idea, based in part on Mackinnon’s crystallographic data.
The above proposal leaves open the question of whether the conformational change is continuous,
as implied in Figure 12.16a, or discrete. The two possibilities give rise to an analog gating of the
membrane current (as in the transistors of an audio amplifier), or a digital, on/off mode (as in
computer circuitry). Our experience with allostery in Chapter 9 shows that the latter option is a
real possibility, and indeed patch-clamp recording showed that most ion channels have just two (or
afew) discrete conductance states. For example, the traces in Figure 12.17b each show a single
channel jumping between a closed state with zero current and an open state, which always gives
roughly the same current.