Learning Objectives:
1. Explain why neurones have a resting potential
2. Predict what will happen to the resting potential when the cell's environment changes
3. Explain the symptoms of a channelopathy that affects the resting potential
ION CHANNELS
The ions move in a direction determined by the electrochemical
gradient across the membrane.
In general, ions will tend to flow from an area of high concentration to
one of low concentration. However, in the presence of a voltage
gradient is possible of there to be no ion flow even with unequal
distributions.
Opening of the ion channel can be achieved either by changing the
voltage across the membrane (e.g. depolarisation or the arrival of an
action potential) or by the binding of a chemical substance to a
receptor in or near the channel.
Types of Channel:
- Voltage-gated (or voltage sensitive) and chemically activated (or ligand-gated) channels.
- The activity of many channels is also modulated by intracellular mechanisms including via the
activation of metabolic receptors or changes in intracellular Ca2+ concentration.
- Some ion channels are not opened by voltage changes or chemical messengers but are directly opened
by mechanical stretch or pressure (e.g. the somatosensory and auditory receptors).
The most important property of ion channels is that they imbue the neurone with electrical excitability
and while they are found in all parts of the neurone, and to a lesser extent in neuroglial cells, they are
also seen in a host of non-neuronal membrane.
All biological membranes, including the neuronal membrane, are composed of a lipid bilayer that has
a high electrical resistance (i.e. ions will not readily flow through it). Thus, to ions move across a
membrane, it is necessary to have either ‘pores’ (ion channels) in the lipid bilayer or ‘carriers’ that will
collect the ions from one side of the membrane and carry them across to the other side where they are
released.
Fundamental Properties of Ion Channel
1. Composed of a number of protein subunits that transverse the membrane and allow ions to cross from
one side to the other- transmembrane pore.
2. The channel so formed must be able to move from a closed to an open state and back, although
intermediate steps may be required.
3. It must be able to open in response to specific stimuli. Most channels possess a sensor of voltage (i.e.
one that moves the resting membrane potential from its resting value of approximately -70 to -80mV
to a less negative value).
Some channels, especially those found at synapse, are not opened by a voltage change but by a
chemical (Ach). These channels have a receptor for that chemical and binding to this receptor
leads to channel opening. Many channels posses sensors along with secondary messenger
molecule (cAMP) leading to a modulation of the ion flow across the membrane that the voltage-
dependent process has produced.
, Activation of the voltage sensor or chemical receptor leads to opening of a ‘gate’ within the channel
which allows ions o flow through the channel. The channel is then closed by either a process of
deactivation, which is simply the reversal of the opening of the gate, or inactivation, which involves a
second gate moving into the channel more slowly than the activation gate moves out so that there is a time
when there is no gate in the channel and ions can flow through it.
Selective Channels
- It allows certain ions through and it achieves this by means of a filter.
- The selectivity filter is based on energetic considerations (thermodynamically) and gives the channel
its name (e.g. sodium channel).
- However, certain channels are non-selective in that they allow many different types of similarly
charges ions through (e.g. Ach cation channel).
The net flow of ions through a channel is termed the current, while the conductance is defined as the
reciprocal of resistance (current/voltage) and represents the ease with which the ions can pass through the
membrane. Permeability, on the other hand, is defined as the rate of transport of a substance or ion through
the membrane for a given concentration difference.
The number and type of ion channel govern the response characteristics of the cell. In the case of
neurones, this is expressed in terms of the rate of action potential generation and its response to synaptic
inputs.
Clinical Disorders of Ion Channels
Frugs can act in different ways to alter the function of the ion channel such as agonism, antagonism or
allosteric modulation.
Various neurological disorders (primary involving muscle) have been found to be caused by mutations
in the sodium and chloride ion channels. These conditions include various forms of myotonia (delayed
relaxation of skeletal muscle following voluntary contraction, i.e. an inability to let go of objects
easily) and various forms of periodic paralyses in which patients develop a transient flaccid weakness
which can be either partial or generalized.
Certain forms of familial hemiplegic migraine and cerebellar dysfunction are associated with
abnormalities in the Ca2+ channel, and some forms of epilepsy may be caused by a disorder of or
exposing of normally non-functioning ion channels. This commonly occurs next to the node of
Ranvier because of central demyelination in multiple
sclerosis and peripheral demyelination in the
Guillain-Barre syndrome, and results in an
impairment in action potential propagation.
In some conditions, antibodies are produced in the
body (sometimes in response to a tumor) which react
with voltage-gated ion channels, producing disorders
in the central nervous system (e.g. limbic
encephalitis and anti-voltage-gated potassium
channels) as well as in the peripheral nervous system
(Lambert-Eaton myasthenic syndrome and anti-
voltage-gated calcium channels).
Resting Membrane Potential
- In this resting state, the neuronal cell membrane is
relatively impermeable to ions.
- The major intracellular ion is potassium, compared to
sodium in the extracellular fluid, and so the natural
1. Explain why neurones have a resting potential
2. Predict what will happen to the resting potential when the cell's environment changes
3. Explain the symptoms of a channelopathy that affects the resting potential
ION CHANNELS
The ions move in a direction determined by the electrochemical
gradient across the membrane.
In general, ions will tend to flow from an area of high concentration to
one of low concentration. However, in the presence of a voltage
gradient is possible of there to be no ion flow even with unequal
distributions.
Opening of the ion channel can be achieved either by changing the
voltage across the membrane (e.g. depolarisation or the arrival of an
action potential) or by the binding of a chemical substance to a
receptor in or near the channel.
Types of Channel:
- Voltage-gated (or voltage sensitive) and chemically activated (or ligand-gated) channels.
- The activity of many channels is also modulated by intracellular mechanisms including via the
activation of metabolic receptors or changes in intracellular Ca2+ concentration.
- Some ion channels are not opened by voltage changes or chemical messengers but are directly opened
by mechanical stretch or pressure (e.g. the somatosensory and auditory receptors).
The most important property of ion channels is that they imbue the neurone with electrical excitability
and while they are found in all parts of the neurone, and to a lesser extent in neuroglial cells, they are
also seen in a host of non-neuronal membrane.
All biological membranes, including the neuronal membrane, are composed of a lipid bilayer that has
a high electrical resistance (i.e. ions will not readily flow through it). Thus, to ions move across a
membrane, it is necessary to have either ‘pores’ (ion channels) in the lipid bilayer or ‘carriers’ that will
collect the ions from one side of the membrane and carry them across to the other side where they are
released.
Fundamental Properties of Ion Channel
1. Composed of a number of protein subunits that transverse the membrane and allow ions to cross from
one side to the other- transmembrane pore.
2. The channel so formed must be able to move from a closed to an open state and back, although
intermediate steps may be required.
3. It must be able to open in response to specific stimuli. Most channels possess a sensor of voltage (i.e.
one that moves the resting membrane potential from its resting value of approximately -70 to -80mV
to a less negative value).
Some channels, especially those found at synapse, are not opened by a voltage change but by a
chemical (Ach). These channels have a receptor for that chemical and binding to this receptor
leads to channel opening. Many channels posses sensors along with secondary messenger
molecule (cAMP) leading to a modulation of the ion flow across the membrane that the voltage-
dependent process has produced.
, Activation of the voltage sensor or chemical receptor leads to opening of a ‘gate’ within the channel
which allows ions o flow through the channel. The channel is then closed by either a process of
deactivation, which is simply the reversal of the opening of the gate, or inactivation, which involves a
second gate moving into the channel more slowly than the activation gate moves out so that there is a time
when there is no gate in the channel and ions can flow through it.
Selective Channels
- It allows certain ions through and it achieves this by means of a filter.
- The selectivity filter is based on energetic considerations (thermodynamically) and gives the channel
its name (e.g. sodium channel).
- However, certain channels are non-selective in that they allow many different types of similarly
charges ions through (e.g. Ach cation channel).
The net flow of ions through a channel is termed the current, while the conductance is defined as the
reciprocal of resistance (current/voltage) and represents the ease with which the ions can pass through the
membrane. Permeability, on the other hand, is defined as the rate of transport of a substance or ion through
the membrane for a given concentration difference.
The number and type of ion channel govern the response characteristics of the cell. In the case of
neurones, this is expressed in terms of the rate of action potential generation and its response to synaptic
inputs.
Clinical Disorders of Ion Channels
Frugs can act in different ways to alter the function of the ion channel such as agonism, antagonism or
allosteric modulation.
Various neurological disorders (primary involving muscle) have been found to be caused by mutations
in the sodium and chloride ion channels. These conditions include various forms of myotonia (delayed
relaxation of skeletal muscle following voluntary contraction, i.e. an inability to let go of objects
easily) and various forms of periodic paralyses in which patients develop a transient flaccid weakness
which can be either partial or generalized.
Certain forms of familial hemiplegic migraine and cerebellar dysfunction are associated with
abnormalities in the Ca2+ channel, and some forms of epilepsy may be caused by a disorder of or
exposing of normally non-functioning ion channels. This commonly occurs next to the node of
Ranvier because of central demyelination in multiple
sclerosis and peripheral demyelination in the
Guillain-Barre syndrome, and results in an
impairment in action potential propagation.
In some conditions, antibodies are produced in the
body (sometimes in response to a tumor) which react
with voltage-gated ion channels, producing disorders
in the central nervous system (e.g. limbic
encephalitis and anti-voltage-gated potassium
channels) as well as in the peripheral nervous system
(Lambert-Eaton myasthenic syndrome and anti-
voltage-gated calcium channels).
Resting Membrane Potential
- In this resting state, the neuronal cell membrane is
relatively impermeable to ions.
- The major intracellular ion is potassium, compared to
sodium in the extracellular fluid, and so the natural
