Biomedical Engineering Reference
In-Depth Information
Several lines of evidence indicate that metabotropic glutamate
receptors (mGluR) play a key role in the mobilization of intra-
cellular Ca
2
+
stores in response to synaptic release of glutamate
(5, 6)
. In culture, astrocytes respond to glutamate with oscillatory
increases in Ca
2
+
and intercellular Ca
2
+
waves propagation
(1)
.
Glutamate released during neuronal activity may reach astrocytic
receptors through synaptic “spillover”
(29, 30)
or ectopic release
(31)
. In addition, neurotransmitters may directly activate astro-
cytes through volume transmission
(32)
.
2.2. Modulatory Role
of Gliotransmitters
Released by
Astrocytes
Although we know that astrocytes sense the neurotransmitters
in extracellular space, we know very little about the conse-
quences of astrocytic receptors activation. In vitro preparations
have shown that astrocytic Ca
2
+
signaling is associated with
release of gliotransmitters. Several of the best studied gliotrans-
mitters include glutamate, ATP, D-serine, TNF-alpha, and arachi-
donic acid metabolites
(3,10,33-35)
(
Fig. 5.1)
. Thus, by sensing
the extracellular neurotransmitter concentration and increasing
intracellular Ca
2
+
, astrocytes may actively participate in the infor-
mation processing in the normal brain.
3. Interface
Between
Astrocytic Endfeet
and the
Vasculatures
Astrocytes send processes to contact not only synapses but also
the vasculature forming specialized endfoot structures in the
astrocyte-vasculature interface (AVI). A variety of channels and
receptors required for interaction between astrocytes and vas-
culatures are clustered in the astrocytic endfoot processes. For
instance, purinergic receptors P2Y2 and P2Y4 as well as gap junc-
tions composed of Cx43 have been shown to be preferentially
expressed in the astrocytic endfeet
(36)
. Accordingly, direct appli-
cation of ATP, electrical stimulation and uncaging evoked astro-
cytic Ca
2
+
waves can propagate along the AVI
(17, 36)
. Increases
of astrocytic Ca
2
+
in the endfeet can activate Ca
2
+
- sensitive
K
+
channels, which is also abundantly expressed in the endfeet
(37)
, and subsequently dilate intracerebral arterioles by increasing
extracellular K
+
concentration in the AVI
(19, 38)
(
Fig. 5.1)
.
4. In Vivo Imaging
of Astrocytic Ca2+
Signaling by
2-Photon Laser
Scanning
Microscopy
(2PLSM)
Due to the technical challenges, imaging astrocytic Ca
2
+
signal-
ing in vivo was only possible after the introduction of 2PLSM
(39)
and the in vivo Ca
2
+
indicator loading techniques
(40, 41)
.
