45
4
in the peripheral nervous system include acetylcholine and noradrenaline. Acetylcholine
is also the neurotransmitter at the neuromuscular junction. In the central nervous system, glutamate, γ-aminobutyric acid (GABA) and glycine are the most abundant neurotransmitters.
Alternatively, synaptic release of so-called neuromodulators activates GPCRs. In this
case, second messengers are generated inside the cell, and these will then open or close ion
channels by interacting with intracellular binding sites on second messenger-activated
(SMOCs, channels activated by second messengers other than cyclic nucleotides) or cyclic
nucleotide-activated ion channels (CNGCs). GPCR signalling activated by neuromodulators is slower than direct neurotransmitter gating through LGICs, and it additionally
a
d
Voltage-gated
Ligand-gated
(intracellular ligand)
c
Ligand-gated
(extracellular ligand)
b
Mechanically gated
+++
−−−
Closed
−−−
+++
Open
Closed
Open
Closed
Open
Closed
Open
. Fig. 4.1 Schematic representation of channel “gating” by a voltage, b mechanical forces and
c, d ligand binding
4.1 · Channels and Transporters