Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

channels and the electrical PROPERTIES of membranes
637
presynaptic
cell
glutamate
polarized
membrane
+ + +
+
– – – –
postsynaptic
cell
Mg 2+
NMDA receptor
+ + +
–
–
–
– – – +
+
+
Na+
AMPA
receptor
glutamate released by
activated presynaptic
nerve terminal opens
AMPA-receptor channels,
allowing Na + influx
that depolarizes
the postsynaptic
membrane
depolarized
membrane
for LTP induction. Such animals exhibit specific deficits in their learning abilities
but behave almost normally otherwise.
How do NMDA receptors mediate LTP? The answer is that these channels,
when open, are highly permeable to Ca 2+ , which acts as an intracellular signal in
the postsynaptic cell, triggering a cascade of changes that are responsible for LTP.
Thus, LTP is prevented when Ca 2+ levels are held artificially low in the postsynaptic
cell by injecting the Ca 2+ chelator EGTA into it, and LTP can be induced by artificially
raising intracellular Ca 2+ levels in the cell. Among the long-term changes
that increase the sensitivity of the postsynaptic cell to glutamate is the insertion of
new AMPA receptors into the plasma membrane (Figure 11–44). In some forms
of LTP, changes occur in the presynaptic cell as well, so that it releases more glutamate
than normal when it is activated subsequently.
If synapses were capable only of LTP they would quickly become saturated,
and thus be of limited value as an information-storage device. In fact, they also
exhibit long-term depression (LTD), with the long-term effect of reducing the
number of AMPA receptors in the post-synaptic membrane. This feat is accomplished
by degrading AMPA receptors after their selective endocytosis. Surprisingly,
LTD also requires NMDA receptor activation and a rise in Ca 2+ . How does
Ca 2+ trigger opposite effects at the same synapse? It turns out that this bidirectional
control of synaptic strength depends on the magnitude of the rise in Ca 2+ :
high Ca 2+ levels activate protein kinases and LTP, whereas modest Ca 2+ levels activate
protein phosphatases and LTD.
There is evidence that NMDA receptors have an important role in synaptic
plasticity and learning in other parts of the brain, as well as in the hippocampus.
Moreover, they have a crucial role in adjusting the anatomical pattern of synaptic
connections in the light of experience during the development of the nervous
MBoC6 m11.42/11.45
system.
Thus, neurotransmitters released at synapses, besides relaying transient electrical
signals, can also alter concentrations of intracellular mediators that bring
about lasting changes in the efficacy of synaptic transmission. However, it is still
uncertain how these changes endure for weeks, months, or a lifetime in the face
of the normal turnover of cell constituents.
Summary
Ion channels form aqueous pores across the lipid bilayer and allow inorganic ions
of appropriate size and charge to cross the membrane down their electrochemical
gradients at rates about 1000 times greater than those achieved by any known
transporter. The channels are “gated” and usually open transiently in response to
a specific perturbation in the membrane, such as a change in membrane potential
(voltage-gated channels), or the binding of a neurotransmitter to the channel
(transmitter-gated channels).
K + -selective leak channels have an important role in determining the resting
membrane potential across the plasma membrane in most animal cells.
depolarization removes
Mg 2+ block from NMDAreceptor
channel, which
(with glutamate bound)
allows Ca 2+ to enter the
postsynaptic cell
– –
–
+
+
+
Ca 2+
increased Ca 2+ in the cytosol
induces postsynaptic cell to
insert new AMPA receptors in the
plasma membrane, increasing
the cell's sensitivity to
glutamate
+ + +
+ +
– – – – –
+
–
Figure 11–44 The signaling events in longterm
potentiation. Although not shown,
transmission-enhancing changes can also
occur in the presynaptic nerve terminals in
LTP, which may be induced by retrograde
signals from the postsynaptic cell.