Biomedical Engineering Reference
In-Depth Information
charging periods lasting a few ms
(2)
. Cellular excitability (or sig-
naling) depends on ionic distribution across the cell membrane.
The cell maintains a large difference in ionic distribution (
10:1)
between the intra and extracellular compartments: higher con-
centrations of sodium (Na
+
), calcium (Ca
2
+
), and chloride (Cl
−
)
ions outside and higher, but unbalanced, concentration of potas-
sium (K
+
) ions inside. Since the resting cell membrane is only
marginally leaky to ions, passage of ions between intra and extra-
cellular compartments is mediated predominantly by ion chan-
nels and pumps
(13)
. Both voltage- and ligand-gated ion chan-
nels allow ion movement down large chemical gradients, whereas
ion pumps (e.g., Na
+
/K
+
ATPase) help restore the ionic distri-
butions (back to that in the resting cell) by moving ions against
large chemical gradients. Restoration of ion gradients (requiring
energy input) is needed to keep neurons ready to discharge (or
fire) whenever needed.
At rest, the cell membrane can be considered to be nearly
impermeable to Na
+
ions with a membrane potential of approx-
imately -70 mV (resting potential). Upon depolarization, how-
ever, the membrane becomes almost freely permeable to Na
+
ions and the potential is nearly reversed in an action potential
(i.e., when the neuron has fired). Therefore, complete depolariza-
tion of the pre-synaptic axon (
∼
1 mm long) can be approximated
by increased permeability of Na
+
ions across the cell membrane.
However, complementary roles of K
+
and Ca
2
+
voltage-gated ion
channels are important. Delayed increase in K
+
conductance (in
conjunction with delayed decrease in Na
+
conductance) causes
the membrane potential of the pre-synaptic neuron to ultimately
move back toward the resting value following depolarization
(14)
. Rapid pre-synaptic Ca
2
+
>
∼
μ
M) within 1-2 ms
after onset of depolarization triggers vesicles to release glutamate
into the extracellular space
(15)
.
Glutamate discharge into the synaptic cleft (20 nm wide) is
a vital step in transmission of the pre-synaptic signal on to post-
synaptic elements
(2)
. Depolarization of the post-synaptic neuron
is initiated by raising extracellular glutamate concentration (from
nM to
influx (
200
M). Glutamate activation, mediated by ligand-gated ion
channels on post-synaptic elements, occurs within 10 ms
(16)
.
During transient binding of glutamate with these ionotropic
receptors, Na
+
ions enter post-synaptic dendrites. The pyramidal
dendritic branching patterns (spanning several mm) are thought
to play a role in amplification of post-synaptic depolarization
(1, 2)
.
What is the fate of extracellular glutamate after pre-synaptic
release? There is a large glutamate concentration gradient
between pre-synaptic and extracellular compartments (mM vs.
nM)
(17)
. Also, there is a high density of glutamate receptors
on astrocytic endfeet
(13)
. Together, these favor extracellular;
glutamate release followed by glial uptake of glutamate (which
μ
