Ion Channels and the electrical properties of membranes'

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Chapter 11
Lecture 27 pages 631-646

• Ion Channels and the electrical properties of
  membranes.

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• Ion channels
• Multipass transmembrane proteins with
  alpha-helical transmembrane domains organized
  into a hydrophilic channel.
• Selects ions by size and charge. The selectivity
  arises because the channel narrows and forces the
  ions to come in contact with amino acid
  side-chains lining the channel.
• Transport of ions is 100,000 times faster than
  the fastest carrier protein.
• Limited to passive transport.

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Ion channels are ion-selective because of narrow
region called the selectivity filter.
side view
R
R
R
top view - each circle represents an end-on view
of an alpha-helix and the R-groups radiating
outwards are amino acid side chains.
R
R
R
R
R
R
R
R
R
R
R
R
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We can anticipate that the red R-groups are
hydrophobic and the blue R-groups are
hydrophilic.
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
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How can a K channel discriminate between K and
Na since they both have the same charge and Na
is smaller than K?
The answer as the ion passes through the
selectivity filter, the ion must shed water.
Carbonyl oxygens with partial negative charge can
take the place of water for K but Na is too
small. Hence, Na favors remaining associated
with water and hydrated ion is too large to fit
through the selectivity filter.
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The carbonyl oxygens that line the selectivity
filter are presented as parts of loops. They
are available because they are not tied up in
hydrogen bonding with other nitrogens in the
peptide backbone.
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Ion channels fluctuate between open and closed
state to regulate ion flow.

• Voltage-gated channels respond to the membrane
  potential.
• Ligand-gated channels respond to association of
  small molecules called ligands.
• Mechanically gated channels respond to movement.

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Understanding the electrical properties of
membranes.
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Establishing a resting membrane potential in
animal cells results from the coordinated action
of carrier proteins and ion channels.
1. Na-K ATPase concentrates K inside the cell
and Na outside (active transport). 2. K leak
channels allow K to diffuse out of the cells,
down the concentration gradient (passive
transport). 3. Negative charge left behind in the
cytoplasm counteracts the efflux of K so only a
very small amount (1/100,000) K leak out. 4. The
efflux of the K is sufficient to generate a
membrane potential of approximately -100 mV -
positive outside and negative inside.
The resting potential is defined as the membrane
potential occurring when there is no net flow of
ions. Cells typically have resting potentials
between -20 and -200 mV. The major contributor
is the K leak channel, but other channels
account for the range of potentials observed.
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Nerve cell.
Dendrites - cell protrusions that receive signals
from axons. Cell body - location of nucleus. Axon
- single long protrusion that sends signal away
from the cell body.
A nerve impulse results from electrical
disturbances in the plasma membrane that spread
from one part of the cell to another. The
electrical disturbance is called an action
potential and it consists of a wave of membrane
depolarization that moves down the axon.
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A threshold depolarization initiates the action
potential.
When a nerve receives a signal, a modest
depolarization of the membrane occurs. If this
depolarization reaches the threshold, all the
voltage-gated Na channels experiencing this
threshold depolarization will open
simultaneously. Na rushes into the cell causing
a rapid and large depolarization of the membrane.
This rapid and large depolarization is the
action potential.
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- - - - -
Outside
Plasma Membrane
Cytoplasm
Time
Outside
- - - - -
Plasma Membrane
Cytoplasm
Red trace shows the change in membrane potential
at a specific site on the axon. This electrical
disturbance is the action potential. The green
trace shows the hypothetical change that would
occur if there were no voltage gated ion channels.
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Voltage-gated channels are the key to an action
potential.
Depolarization to a specific membrane potential
causes the channels to open. This specific
membrane potential can be thought of as the
threshold that must be reached to get the channel
to open.
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The channel opens briefly but then automatically
becomes inactive. It will remain inactive (and
closed) until it is reset by the resting
potential. Only after resetting, can the channel
respond again to a threshold potential.
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The return to the resting potential relies, in
part, on inactivation of the voltage-gated Na
channel.
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Repolarization depends on opening of
voltage-gated K channels open. These open more
slowly than the voltage-gated Na channels so
there is time for the influx of Na to depolarize
the membrane before the efflux of K begins to
repolarize the membrane.
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The voltage-gated Na channel will not respond to
another threshold potential until it has been
subjected to the original negative membrane
potential.
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The channel cycle of closed, opened, inactivated
along the axon results in propagation of the
action potential.
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Initiation of an action potential requires that
something cause the membrane to depolarize to the
threshold potential. The process begins at the
synapse.
presynaptic cell
postsynaptic cell
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Depolarizing the postsynaptic membrane so an
action potential can be initiated. 1.
Neurotransmitter is released from the presynaptic
cell when the action potential arrives at the end
of the terminal branches. 2. Neurotransmitter
diffuses across the synaptic cleft and associates
with ligand-gated Na channels (a.k.a.
transmitter gated Na channels). 4.
Ligand-gated Na channels open and the influx of
Na depolarizes the membrane. 5. If enough
channels open, the threshold potential will be
reached and the action potential will begin as a
result of the opening of voltage-gated Na
channels.
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Another view of how the action potential is
initiated.
The events leading to repolarization are not
shown.
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The changes in membrane potential are achieved by
the movement of very few ions. Hence, the
overall concentrations of potassium and sodium
inside and outside the cell do not change when
various channels open and close. Sodium stays
high outside and potassium stays high inside.
Small fluxes of ions are sufficient to change
potentials.