53
4
channel in the membrane of motor neurons. N-type and R-type VOC channels are
similarly built, and all three types are mainly localized in neurons. They have a synprint
site (synaptic vesicle interaction region) in the second intracellular loop. It binds
SNAREs and thus anchors the channel to the exocytosis machinery involving syntaxin
(t-SNARE) and SNAP25 (v-SNARE). Exocytosis is triggered by interaction of the Ca 2+ -
binding protein synaptotagmin with the SNARE complex that is completely preformed
and ready to secrete vesicle content into the synaptic cleft. In response to an action
potential arriving at the presynapse, the opening of Ca 2+ -channels provides the necessary Ca 2+ -sparks. Physical coupling of the channel to the SNARE complex allows fast
neurotransmitter release. Mutations in the synprint site of VOCs have been found in
patients with human genetic disorders including episodic ataxia and familial hemiplegic
migraine (Berridge 2012).
4.4 Extracellular Ligand-Operated Channels: Neurotransmitter
Receptors
A large family of ion channels is gated by binding of ligands, e.g. neurotransmitters. This
causes either excitatory or inhibitory neurotransmission depending on the ion conductance of the channels. Excitatory receptors are gated by acetylcholine (NAchR), serotonin
(5-HT-3-receptor) and glutamate (NMDA, AMPA and kainite receptors) and allow passage of Na + and Ca 2+ -ions into the cell, inducing membrane depolarization. Glycine- and
GABA-gated channels are Cl − -channels. Their opening increases the negative charge at
the membrane inside the cell, leading to hyperpolarization (as long as the outside concentration of chloride ions is higher than the inside concentration) (see . Fig. 4.5).
a
b
Na +
Ca 2+
Depolarisation
Glutamate
Acetylcholine
Glycine
GABA
Cl −
Hyperpolarisation
a
b
Na +
Ca 2+
Depolarisation
Glutamate
Acetylcholine
Glycine
GABA
Activation (= excitatory
neurotransmission)
Cl −
Hyperpolarisation
Inactivation (= inhibitory
neurotransmission)
. Fig. 4.5 a Glutamate-/acetylcholine-gated cation channel; opening induces membrane depolarization and excitatory neurotransmission; b glycine-/GABA-gated anion channel; opening induces membrane hyperpolarization and inhibitory neurotransmission
4.4 · Extracellular Ligand-Operated Channels: Neurotransmitter Receptors
4
channel in the membrane of motor neurons. N-type and R-type VOC channels are
similarly built, and all three types are mainly localized in neurons. They have a synprint
site (synaptic vesicle interaction region) in the second intracellular loop. It binds
SNAREs and thus anchors the channel to the exocytosis machinery involving syntaxin
(t-SNARE) and SNAP25 (v-SNARE). Exocytosis is triggered by interaction of the Ca 2+ -
binding protein synaptotagmin with the SNARE complex that is completely preformed
and ready to secrete vesicle content into the synaptic cleft. In response to an action
potential arriving at the presynapse, the opening of Ca 2+ -channels provides the necessary Ca 2+ -sparks. Physical coupling of the channel to the SNARE complex allows fast
neurotransmitter release. Mutations in the synprint site of VOCs have been found in
patients with human genetic disorders including episodic ataxia and familial hemiplegic
migraine (Berridge 2012).
4.4 Extracellular Ligand-Operated Channels: Neurotransmitter
Receptors
A large family of ion channels is gated by binding of ligands, e.g. neurotransmitters. This
causes either excitatory or inhibitory neurotransmission depending on the ion conductance of the channels. Excitatory receptors are gated by acetylcholine (NAchR), serotonin
(5-HT-3-receptor) and glutamate (NMDA, AMPA and kainite receptors) and allow passage of Na + and Ca 2+ -ions into the cell, inducing membrane depolarization. Glycine- and
GABA-gated channels are Cl − -channels. Their opening increases the negative charge at
the membrane inside the cell, leading to hyperpolarization (as long as the outside concentration of chloride ions is higher than the inside concentration) (see . Fig. 4.5).
a
b
Na +
Ca 2+
Depolarisation
Glutamate
Acetylcholine
Glycine
GABA
Cl −
Hyperpolarisation
a
b
Na +
Ca 2+
Depolarisation
Glutamate
Acetylcholine
Glycine
GABA
Activation (= excitatory
neurotransmission)
Cl −
Hyperpolarisation
Inactivation (= inhibitory
neurotransmission)
. Fig. 4.5 a Glutamate-/acetylcholine-gated cation channel; opening induces membrane depolarization and excitatory neurotransmission; b glycine-/GABA-gated anion channel; opening induces membrane hyperpolarization and inhibitory neurotransmission
4.4 · Extracellular Ligand-Operated Channels: Neurotransmitter Receptors