476 Chapter 12. Nerve impulses[[Student version, January 17, 2003]]
Today we attribute the observed two-stage dynamics of the sodium conductance under sustained
depolarization to two independent, successive obstructions which a sodium ion must cross. One
of these obstructions opens rapidly upon depolarization, whereas the other closes slowly. The
second process, calledinactivation,involves achannel-inactivating segment,loosely attached to
the sodium channel by a flexible tether (Figure 12.16b), according to a model due to Armstrong
and F. Bezanilla. Under sustained depolarization the channel-inactivating segment eventually enters
the open channel, physically blocking it. Upon repolarization, the segment wanders away, and the
channel is ready to open again.
Several ingenious experiments supported this model. For example, Armstrong found that he
could cleave away the chanel-inactivating segment with enzymes, destroying the inactivation process
but leaving the fast opening process unchanged. Later R. Aldrich and coauthors manufactured
channels in which the flexible linker chain joining the inactivating segment to the channel was shorter
than usual. The modified channels inactivated faster than their natural counterparts: Shortening
the chain made it easier for the inactivation segment to find its docking site by diffusive motion.
12.4 Nerve, muscle, synapse
Another book the size of this one would be needed to explore the ways in which neurons accept
sensory information, perform computation, and stimulate muscle activity. This short section will
at best convey a survey of such a survey, emphasizing links to our discussion of action potentials.
12.4.1 Nerve cells are separated by narrow synapses
Most body tissues consist of cells with simple, compact shapes. In contrast, nerve cells are large,
have complex shapes, and are intertwined with each other to such an extent that by the late
nineteenth century many anatomists still thought of the brain as a continuous mass of fused cells
and fibers, and not as a collection of distinct cells. The science of neuroanatomy could not begin
until 1873, when Camillo Golgi developed a silver-impregnation technique which stained only a few
nerve cells in a sample (typically 1%), but stained the selected cells completely. Thus the stained
cells could stand out from the intertwining mass of neighboring cells, and their full extent could be
mapped.
Improving Golgi’s technique, Santiago Ram ́on y Cajal drew meticulous and breathtaking pic-
tures of entire neurons (Figure 12.20). Cajal argued in 1888 that neurons were in fact distinct
cells. Golgi himself never regarded the neuron doctrine as proved.^12 Indeed, the definitive proof
required the development of electron microscopy to see the narrow synapse separating adjoining
neurons. Figure 12.21 shows a modern view of this region. One nerve cell’s axon ends at another’s
dendrite (or on a dendritic spine attached to the dendrite). The cells interact when an impulse
travels to the end of the axon and stimulates the next cell’s dendrite across a narrow (10–30nm
wide) gap, thesynaptic cleft (Figure 12.21). Thus, information flows from thepresynaptic(axon)
side of the cleft to thepostsynaptic(dendrite) side. A similar synapse joins a motor nerve axon to
the muscle fiber whose contraction it controls.
(^12) Golgi was right to be cautious: His method doesnotalways stain whole neurons; it often misses fine processes,
especially axons.