Page 95 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Acetylcholine and Cholinergic different subunits. They are similar in that they
Transmission are both ionotropic receptors, i.e., they act as
cholinoceptors and cation channels at the
+
Acetylcholine (ACh) serves as a neurotransmit- same time. ACh binding leads to rapid Na and
ter not only at motor end plates (! p. 56) and Ca influx and in early (rapid) excitatory post-
2+
in the central nervous system, but also in the synaptic potentials (EPSP; ! p. 50ff.), which
autonomic nervous system, ANS (! p. 78ff.), trigger postsynaptic action potentials (AP)
where it is active once they rise above threshold (! A, left
! in all preganglionic fibers of the ANS;
panel).
Autonomic Nervous System (ANS) nerve endings (sweat glands). (metabotropic receptors). 2+ influx
M-cholinoceptors (M 1–M 5) indirectly affect
! in all parasympathetic postganglionic nerve
endings;
synaptic transmission through G-proteins
! and in some sympathetic postganglionic
M 1-cholinoceptors occur mainly on auto-
nomic ganglia (! A), CNS, and exocrine gland
Acetylcholine synthesis. ACh is synthesized in the
cells. They activate phospholipase C" (PLC")
cytoplasm of nerve terminals, and acetyl coenzyme
via G q protein in the postganglionic neuron.
A (acetyl-CoA) is synthesized in mitochondria. The
and inositol tris-phosphate (IP 3) and diacyl-
reaction acetyl-CoA + choline is catalyzed by choline
glycerol (DAG) are released as second mes-
acetyltransferase, which is synthesized in the soma
and reaches the nerve terminals by axoplasmic trans-
sengers (! p. 276) that stimulate Ca
extracellular fluid by way of a carrier, this is the rate-
signal transmission is modulated by the late
limiting step of ACh synthesis.
EPSP as well as by co-transmitting peptides
3 port (! p. 42). Since choline must be taken up from and a late EPSP (! A, middle panel). Synaptic
Acetylcholine release. Vesicles on presynaptic
that trigger peptidergic EPSP or IPSP (! A, right
nerve terminals empty their contents into the panel).
synaptic cleft when the cytosolic Ca 2+ concen- M 2-cholinoceptors occur in the heart and
tration rises in response to incoming action function mainly via a G i protein (! p. 274 ff.).
+
potentials (AP) (! A, p. 50ff.). Epinephrine and The G i protein opens specific K channels lo-
norepinephrine can inhibit ACh release by cated mainly in the sinoatrial node, atri-
stimulating presynaptic α 2-adrenoceptors oventricular (AV) node, and atrial cells,
(! p. 84). In postganglionic parasympathetic thereby exerting negative chronotropic and
fibers, ACh blocks its own release by binding to dromotropic effects on the heart (! B). The G i
presynaptic autoreceptors (M-receptors; see protein also inhibits adenylate cyclase, thereby
below), as shown in B. reducing Ca 2+ influx (! B).
ACh binds to postsynaptic cholinergic re- M 3-cholinoceptors occur mainly in smooth
ceptors or cholinoceptors in autonomic gan- muscles. Similar to M 1-cholinoceptors (! A,
glia and organs innervated by parasympa- middle panel), M 3-cholinoceptors trigger con-
thetic fibers, as in the heart, smooth muscles tractions by stimulating Ca 2+ influx (! p. 70).
(e.g., of the eye, bronchi, ureter, bladder, geni- However, they can also induce relaxation by
2+
tals, blood vessels, esophagus, and gastroin- activating Ca -dependent NO synthase, e.g., in
testinal tract), salivary glands, lacrimal glands, endothelial cells (! p. 278).
and (sympathetically innervated) sweat Termination of ACh action is achieved by
glands (! p. 80ff.). Cholinoceptors are ni- acetylcholinesterase-mediated cleavage of ACh
cotinic (N) or muscarinic (M). N-cholinocep- molecules in the synaptic cleft (! p. 56). Ap-
tors (nicotinic) can be stimulated by the alka- proximately 50% of the liberated choline is re-
loid nicotine, whereas M-cholinoceptors (mus- absorbed by presynaptic nerve endings (! B).
carinic) can be stimulated by the alkaloid Antagonists. Atropine blocks all M-cholino-
mushroom poison muscarine. ceptors, whereas pirenzepine selectively
Nerve-specific N N-cholinoceptors on auto- blocks M 1-cholinoceptors, tubocurarine blocks
nomic ganglia (! A) differ from muscle- N M-cholinoceptors (! p. 56), and trimetaphan
specific N M-cholinoceptors on motor end blocks N N-cholinoceptors.
82 plates (! p. 56) in that they are formed by
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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