55
4
The function of many of these receptors is not yet known. However, the structure of all
members of this family is very similar. They show an arrangement of six transmembrane
segments with a pore loop between segments S5 and S6. This is similar to the subdomains
of VOCs. In TRP channels, four independent channel proteins oligomerize to form the
complete channel. This involves homo-oligomerization but also hetero-oligomerization of
members of different subfamilies resulting in a great variety of possible TRP channels.
Members of TRPC, TRPV and TRPM families differ in their intracellular N-terminal and
C-terminal domains. All contain a so-called TRP box in the intracellular C-terminal part.
TRPC and TRPV family members are then characterized by their possession of ankyrin
repeats in the intracellular N-terminal region. TRPM family members do not have such
ankyrin repeats. Their C-terminal intracellular domains are very large and often have
enzymatic domains, e.g. protein kinase or ADP-ribose pyrophosphatase domains
(Berridge 2012).
Take-Home Messages
5 Ion channels allow passage of ions through membranes according to their concentration gradient and without the use of energy. Transporters actively move
ions through membranes against their concentration gradient using energy.
5 An electrochemical gradient exists in all cells of the body. It is maintained by the
action of the 3Na + /2 K + - ATPase establishing an opposite concentration gradient across the membrane for K + -ions of 140 mM inside versus 4 mM outside
the cell and for Na + -ions of 12 mM inside versus 150 mM outside the cell. In
excitable cells, changes in the membrane potential are used for electrochemical signalling.
5 Voltage-gated ion channels (VOCs) open or close in response to changes in
the membrane potential leading to depolarization or hyperpolarization of the
membrane. These channels conduct Na + -, K + - or Ca 2+ -ions, and they harbour a
central pore for ion passage, a voltage-sensing helix moving within the membrane according to the membrane potential and a plug that closes the channel
after opening.
5 For excitation-contraction coupling at the neuromuscular junction, Ca 2+ -entry
channels are activated in response to action potentials travelling down the
motoneuron. Ca 2+ -influx into the presynapse allows release of the neurotransmitter acetylcholine (AC). AC binds to NAchRs on the muscle cells, starting
membrane depolarization. This finally activates L-type voltage-gated channels on the muscle cell plasma membrane that directly interact with ryanodine receptors on the membrane of the sarcoplasmic reticulum mediating
Ca 2+ release for muscle contraction.
5 Receptor-operated ion channels are activated by ligands, for instance, neurotransmitters. They include glycine- and GABA-gated Cl — channels and the
nicotinic acetylcholine receptor (NAchR) of the pLIC family and glutamate
receptors.
5 TRP channels represent a large family of channel proteins. They are involved
in perception of temperature, taste, pain and mechanical stimuli and conduct
cations, including Na + , K + and Ca 2+ .
4.5 · TRP Channels
4
The function of many of these receptors is not yet known. However, the structure of all
members of this family is very similar. They show an arrangement of six transmembrane
segments with a pore loop between segments S5 and S6. This is similar to the subdomains
of VOCs. In TRP channels, four independent channel proteins oligomerize to form the
complete channel. This involves homo-oligomerization but also hetero-oligomerization of
members of different subfamilies resulting in a great variety of possible TRP channels.
Members of TRPC, TRPV and TRPM families differ in their intracellular N-terminal and
C-terminal domains. All contain a so-called TRP box in the intracellular C-terminal part.
TRPC and TRPV family members are then characterized by their possession of ankyrin
repeats in the intracellular N-terminal region. TRPM family members do not have such
ankyrin repeats. Their C-terminal intracellular domains are very large and often have
enzymatic domains, e.g. protein kinase or ADP-ribose pyrophosphatase domains
(Berridge 2012).
Take-Home Messages
5 Ion channels allow passage of ions through membranes according to their concentration gradient and without the use of energy. Transporters actively move
ions through membranes against their concentration gradient using energy.
5 An electrochemical gradient exists in all cells of the body. It is maintained by the
action of the 3Na + /2 K + - ATPase establishing an opposite concentration gradient across the membrane for K + -ions of 140 mM inside versus 4 mM outside
the cell and for Na + -ions of 12 mM inside versus 150 mM outside the cell. In
excitable cells, changes in the membrane potential are used for electrochemical signalling.
5 Voltage-gated ion channels (VOCs) open or close in response to changes in
the membrane potential leading to depolarization or hyperpolarization of the
membrane. These channels conduct Na + -, K + - or Ca 2+ -ions, and they harbour a
central pore for ion passage, a voltage-sensing helix moving within the membrane according to the membrane potential and a plug that closes the channel
after opening.
5 For excitation-contraction coupling at the neuromuscular junction, Ca 2+ -entry
channels are activated in response to action potentials travelling down the
motoneuron. Ca 2+ -influx into the presynapse allows release of the neurotransmitter acetylcholine (AC). AC binds to NAchRs on the muscle cells, starting
membrane depolarization. This finally activates L-type voltage-gated channels on the muscle cell plasma membrane that directly interact with ryanodine receptors on the membrane of the sarcoplasmic reticulum mediating
Ca 2+ release for muscle contraction.
5 Receptor-operated ion channels are activated by ligands, for instance, neurotransmitters. They include glycine- and GABA-gated Cl — channels and the
nicotinic acetylcholine receptor (NAchR) of the pLIC family and glutamate
receptors.
5 TRP channels represent a large family of channel proteins. They are involved
in perception of temperature, taste, pain and mechanical stimuli and conduct
cations, including Na + , K + and Ca 2+ .
4.5 · TRP Channels