54
4
Despite having opposing effects on the membrane potential, the excitatory NAchR and
5-HT3 (serotonin) receptors and the inhibitory glycine and GABA A receptors belong to
the same family of pentameric ligand-gated ion channels (pLICs). The genes encoding
them have evolved from bacterial precursors. However, bacterial pLICs and eukaryotic
channels have a different extracellular structure. In eukaryotic channel proteins, the extracellular part is characterized by a highly conserved arrangement of two cysteines forming
an intramolecular disulphide bridge. Therefore, they are also called cysteine-loop receptors (Nys et al. 2013).
4.5 TRP Channels
Transient receptor potential ion channels represent a large protein family of channel proteins, encoded by 13 different genes in the worm Caenorhabditis elegans and over 30 genes
in mammals. They are involved in perception of taste, temperature, pain and mechanical
stimuli. The family name is derived from the Drosophila TRP channels that mediate visual
signalling in fly photoreceptor cells. In contrast to mammalian rhodopsin signalling via
activation of transducin and cGMP phosphodiesterase, in flies a G q protein is coupled to
rhodopsin. This activates phospholipase C, which hydrolyses phosphoinositol-4, 5-phosphate PI(4,5)P2. The products DAG and IP3 then, by a still debated biochemical mechanism, lead to opening of TRP channels, which allow Ca 2+ -influx and membrane
depolarization of photoreceptor cells of the fly eye. In a fly mutant with a defect in this
TRP channel, the normally stable action potential after light exposure was only “transient”; hence, the name “transient receptor potential ion channels” was given.
All TRP channels are permeable for cations, including Na + , K + and Ca 2+ , with more or
less selectivity for the respective ion. They are divided into six subfamilies, including the
canonical TRPs (TRPC), vanilloid TRPs (TRPV), melastatin-related TRPs (TRPM), polycystins (TRPP), mucolipin TRPs (TRPML) and TRPA, which can sense mechanical stimuli, temperature and pain (. Fig. 4.6), (Berridge 2012).
N
C
Ca 2+ or Na +
TRPC
TRPV
TRPM
TRPP
TRPML
TRPA
(Canonical)
(Vanilloid)
(Melastatin related)
(Polycystins)
(Mucolipins)
(Mechano, temperature, pain)
cytosol
TRP box
N
C
. Fig. 4.6 Schematic representation of transmembrane domain structure and overview of TRP
channel family members; in structure, common TRP box, light grey; ion-conducting pore, red arrow;
diverse N- and C-terminal regions, dotted lines
Chapter 4 · Ion Channels
4
Despite having opposing effects on the membrane potential, the excitatory NAchR and
5-HT3 (serotonin) receptors and the inhibitory glycine and GABA A receptors belong to
the same family of pentameric ligand-gated ion channels (pLICs). The genes encoding
them have evolved from bacterial precursors. However, bacterial pLICs and eukaryotic
channels have a different extracellular structure. In eukaryotic channel proteins, the extracellular part is characterized by a highly conserved arrangement of two cysteines forming
an intramolecular disulphide bridge. Therefore, they are also called cysteine-loop receptors (Nys et al. 2013).
4.5 TRP Channels
Transient receptor potential ion channels represent a large protein family of channel proteins, encoded by 13 different genes in the worm Caenorhabditis elegans and over 30 genes
in mammals. They are involved in perception of taste, temperature, pain and mechanical
stimuli. The family name is derived from the Drosophila TRP channels that mediate visual
signalling in fly photoreceptor cells. In contrast to mammalian rhodopsin signalling via
activation of transducin and cGMP phosphodiesterase, in flies a G q protein is coupled to
rhodopsin. This activates phospholipase C, which hydrolyses phosphoinositol-4, 5-phosphate PI(4,5)P2. The products DAG and IP3 then, by a still debated biochemical mechanism, lead to opening of TRP channels, which allow Ca 2+ -influx and membrane
depolarization of photoreceptor cells of the fly eye. In a fly mutant with a defect in this
TRP channel, the normally stable action potential after light exposure was only “transient”; hence, the name “transient receptor potential ion channels” was given.
All TRP channels are permeable for cations, including Na + , K + and Ca 2+ , with more or
less selectivity for the respective ion. They are divided into six subfamilies, including the
canonical TRPs (TRPC), vanilloid TRPs (TRPV), melastatin-related TRPs (TRPM), polycystins (TRPP), mucolipin TRPs (TRPML) and TRPA, which can sense mechanical stimuli, temperature and pain (. Fig. 4.6), (Berridge 2012).
N
C
Ca 2+ or Na +
TRPC
TRPV
TRPM
TRPP
TRPML
TRPA
(Canonical)
(Vanilloid)
(Melastatin related)
(Polycystins)
(Mucolipins)
(Mechano, temperature, pain)
cytosol
TRP box
N
C
. Fig. 4.6 Schematic representation of transmembrane domain structure and overview of TRP
channel family members; in structure, common TRP box, light grey; ion-conducting pore, red arrow;
diverse N- and C-terminal regions, dotted lines
Chapter 4 · Ion Channels