Biomedical Engineering Reference
In-Depth Information
Presynaptic
Acetyl CoA
+
Cho
AC
h
VAChT
nAChRs
M
2
, M
4
M
2
, M
4
mAChRs
Ca
2+
AChE
ACh
acetate
M
1
, M
3
, M
5
M
2
, M
4
M
1
, M
3
, M
5
M
2
, M
4
mAChRs
nAChRs
(A)
Postsynaptic
(B)
Acetyl CoA
+
Cho
AC
h
VAChT
M
2
, M
4
Gi
—
+
M
2
,
M
4
AChE
AChE
ACh
ACh
Na
+
Ca
2+
Na
+
Ca
2+
Na
+
Ca
2+
acetate
acet
a
te
M
1
, M
3
, M
5
M
2
, M
4
M
1
, M
3
, M
5
M
2
, M
4
Gi
Gq
÷
+
AC
PLC
Gs
AT P
PIP2
IP3 + DAG
cAMP
(C)
(D)
FIGURE 16.4
The cholinergic synapse and the events during synaptic i ring. (A) In the presynaptic ter-
minal, acetylcholine (ACh) is synthesized by “choline acetyltransferase” (ChAT) through acetylation of
the precursor choline (Cho), the source of the acetyl groups being acetyl Coenzyme A (acetyl CoA). The
synthesized ACh is packaged into synaptic vesicles by uptake by the vesicular ACh transporter (VAChT).
(B) Upon stimulation of the presynaptic neuron, cytoplasmic Ca
2+
concentrations are elevated due to the inl ux
of the dication trough voltage-dependent calcium channels (VDCCs), and this causes the ACh-containing
vesicles to fuse with the plasma membrane and release ACh into the synaptic cleft. (C) Here, ACh exerts its
effects via activation of mAChRs and nAChRs. Activation of the postsynaptic nAChRs and mAChRs elicits
the fast excitatory and the slow metabolic signaling of ACh, respectively, whereas activation of presynaptic
receptors inhibits or augments the synaptic release of ACh, thus constituting negative and positive feedback
mechanisms. Concurrently with its binding to the receptors, ACh signaling is being terminated by “acetylcho-
linesterase” (AChE) and “butyrylesterase,” the two enzymes in the synaptic cleft, which converts ACh back
to Cho. Furthermore, the choline transporter (CHT) is transported from the inside of the presynaptic terminal
to the plasma membrane. (D) Having reached the membrane, CHT transports Cho back into the presynaptic
terminal, where it once again is used in the synthesis of ACh. With the degradation of ACh and the subsequent
removal of Cho from the synaptic cleft, the cholinergic neuron returns to its resting state.
