44
4
What You Will Learn in This Chapter
In this chapter we explain the molecular architecture and function of several ion channels.
These include voltage and neurotransmitter gated ion channels as well as channels that are
gated by binding of second messengers to intracellular sites of ion channels. You will also
be briefly introduced to the large family of “transient receptor potential” (TRP) ion channels.
To illustrate the function of ion channels in a physiological context we describe excitationcontraction coupling at the neuromuscular junction in more detail.
4.1 Channels and Transporters
Biological membranes are lipid bilayers. They are not permeable for charged molecules,
even if those are small, like Ca 2+ , K + , Na + and Cl − -ions. An exchange of ions between the
cell interior and the exterior requires dedicated transport molecules. Therefore, eukaryotic cells are equipped with large numbers of transmembrane proteins that function either
as transporters or as ion channels.
Transporters actively move ions through membranes against their concentration gradient. This requires energy, e.g. from ATP hydrolysis. Ion channels, on the other hand,
allow passive passage of ions along their concentration gradient. They are inserted into
membranes in such a way that they build small pores, which expose a hydrophilic surface
at their inside. These channels are regulated in several ways, and they exhibit specificity for
specific ions. In the most extreme case, they are almost constitutively open. In this situation, the ion concentration on either side of the membrane will adjust towards a biophysical equilibrium (dependent on the concentration of the ions and their charge as well
as the given distribution of all other charged molecules across the membrane).
However, the opening and closing of most ion channels occurs in a regulated manner.
Such ion channels are “gated” and usually only open in response to a change in membrane
voltage (voltage-gated ion channels), in response to binding of a ligand (ligand-gated ion
channels) or after physical stimulation (e.g. mechanically gated ion channels) (see
. Fig. 4.1).
Ligands for ion channels can be second messengers (e.g. cAMP, Ca 2+ ) or neurotransmitters (e.g. acetylcholine, glutamate). Many plant-derived drugs target ion channels
that are involved in neurotransmission, the conductance of signals from the axon of one
neuron to a dendrite of another neuron via a chemical synapse. This also includes neurotransmission from motor neurons to muscle cells at neuromuscular junctions. During
this process, changes in voltage, or action potentials, from a presynaptic neuron are converted into a chemical signal at the synapse. The presynaptic neuron releases chemical
neurotransmitters into the synaptic cleft. These neurotransmitters then bind to receptors
at the postsynaptic membrane of dendrites of the next neuron. This directly opens ion
channels on the postsynapse and induces ion influx or efflux according to the ion
concentrations on either side of the membrane. In this way, the membrane potential of
the postsynaptic membrane changes, converting the chemical signal that the postsynaptic membrane had received into an electrical signal that will be further transmitted
within the postsynaptic neuron. In such a way, neurotransmitters “gate”, meaning open
or close, ligand-gated ion channels (LGICs or LICs). They directly evoke a very fast electrophysiological response in the postsynaptic membrane. The major neurotransmitters
Chapter 4 · Ion Channels
4
What You Will Learn in This Chapter
In this chapter we explain the molecular architecture and function of several ion channels.
These include voltage and neurotransmitter gated ion channels as well as channels that are
gated by binding of second messengers to intracellular sites of ion channels. You will also
be briefly introduced to the large family of “transient receptor potential” (TRP) ion channels.
To illustrate the function of ion channels in a physiological context we describe excitationcontraction coupling at the neuromuscular junction in more detail.
4.1 Channels and Transporters
Biological membranes are lipid bilayers. They are not permeable for charged molecules,
even if those are small, like Ca 2+ , K + , Na + and Cl − -ions. An exchange of ions between the
cell interior and the exterior requires dedicated transport molecules. Therefore, eukaryotic cells are equipped with large numbers of transmembrane proteins that function either
as transporters or as ion channels.
Transporters actively move ions through membranes against their concentration gradient. This requires energy, e.g. from ATP hydrolysis. Ion channels, on the other hand,
allow passive passage of ions along their concentration gradient. They are inserted into
membranes in such a way that they build small pores, which expose a hydrophilic surface
at their inside. These channels are regulated in several ways, and they exhibit specificity for
specific ions. In the most extreme case, they are almost constitutively open. In this situation, the ion concentration on either side of the membrane will adjust towards a biophysical equilibrium (dependent on the concentration of the ions and their charge as well
as the given distribution of all other charged molecules across the membrane).
However, the opening and closing of most ion channels occurs in a regulated manner.
Such ion channels are “gated” and usually only open in response to a change in membrane
voltage (voltage-gated ion channels), in response to binding of a ligand (ligand-gated ion
channels) or after physical stimulation (e.g. mechanically gated ion channels) (see
. Fig. 4.1).
Ligands for ion channels can be second messengers (e.g. cAMP, Ca 2+ ) or neurotransmitters (e.g. acetylcholine, glutamate). Many plant-derived drugs target ion channels
that are involved in neurotransmission, the conductance of signals from the axon of one
neuron to a dendrite of another neuron via a chemical synapse. This also includes neurotransmission from motor neurons to muscle cells at neuromuscular junctions. During
this process, changes in voltage, or action potentials, from a presynaptic neuron are converted into a chemical signal at the synapse. The presynaptic neuron releases chemical
neurotransmitters into the synaptic cleft. These neurotransmitters then bind to receptors
at the postsynaptic membrane of dendrites of the next neuron. This directly opens ion
channels on the postsynapse and induces ion influx or efflux according to the ion
concentrations on either side of the membrane. In this way, the membrane potential of
the postsynaptic membrane changes, converting the chemical signal that the postsynaptic membrane had received into an electrical signal that will be further transmitted
within the postsynaptic neuron. In such a way, neurotransmitters “gate”, meaning open
or close, ligand-gated ion channels (LGICs or LICs). They directly evoke a very fast electrophysiological response in the postsynaptic membrane. The major neurotransmitters
Chapter 4 · Ion Channels