Biomedical Engineering Reference
In-Depth Information
back into the perisynaptic processes and supplement ATP pro-
duced by local glycolysis during periods of intense glutamate
uptake. Thus, a possible function of astrocytic Ca
2
+
signaling
evoked during synaptic activity may be to link energy metabolism
in processes and cell body by activating oxidative-phosphorylation
in mitochondria located distant to the perisynaptic processes.
6.3. Energy
Consumption by
Astrocytes During
Neural Activation
Several reviews have proposed that astrocytes only account for
5% of the total energy budget consumed in rodents and about
6% in humans
(66)
. These estimations were based on calcula-
tion of known properties of channels and synapses in neurons
and astrocytes
(66)
. In contrast, studies using in vivo nuclear
magnetic resonance spectroscopy indicate that astrocytes con-
tribute to 15% to 30% of total oxidative metabolism in the brain
(67, 68)
. The prior calculations may neglect many of the energy
requiring functions of protoplasmic astrocytes
(66)
. In addition
to glutamate uptake, multiple ATP consuming processes are acti-
vated in astrocytes during neural activation. For instance, restor-
ing astrocytic Ca
2
+
concentrations following mGluRs mediated
Ca
2
+
mobilization requires activation of both plasma membrane
Ca
2
+
-ATPase and ER Ca
2
+
-ATPase
(69)
. Furthermore, astro-
cytes buffer at least, in part, extracellular K
+
by active uptake
of K
+
through Na
+
-K
+
-ATPase. Astrocytes are the principle cell
type responsible for water homeostasis and clearance of tissue
swelling during episodes of intense synaptic activity likely requires
increased metabolism
(70)
. Moreover, Ca
2
+
dependent activa-
tion of PLA2 results in release of arachidonic acid, which in turn
requires new lipid synthesis. In addition to this energy requir-
ing supportive function of astrocytes, astrocytic Ca
2
+
signaling
likely evokes downstream effects that increase energy demands of
both neurons and other non-neuronal cells. Intercellular astro-
cytic Ca
2
+
signaling is mediated by ATP release from astrocytes
(71)
. ATP is, in addition to its function as an energy metabo-
lite, an important gliotransmitter that triggers Ca
2
+
signaling in
surrounding astrocytes
(33)
, neurons
(72)
, microglia
(73)
and
smooth muscle cells
(19)
. Normalization of Ca
2
+
in all of these
cell types occurs through activation of Ca
2
+
-ATPases. Conversely,
hydrolysis of extracellular ATP results in accumulation of adeno-
sine, which reduces release of glutamate and thereby dampens
energy demands. The notion that astrocytic Ca
2
+
signaling is an
energy requiring process initiated during synaptic activity finds
support in the observation that inhibition of postsynaptic activity
by application of CNQX/APV and TBOA failed to block changes
in NADH signaling evoked during intense electrical stimulation
in brain slice preparation
(74)
. Glycolytic metabolism was shown
not to play an essential role in the CNQX/APV resistant NADH
changes
(74)
, indicating that astrocytic Ca
2
+
increases most sig-
nificantly affect oxidative- phosphorylation.
