ACTION POTENTIALS
The action potential is mediated by ion channels.
There are many ion channels present in the membrane.
The main ones are sodium and potassium channels.
There are many other ion channels involved in neurons and
they all play a part in shaping the action potential.
Leak K Channels
- 4 transmembrane domains.
- 2 pore forming domains
- Not voltage gated. They are open all the time.
- Leak channels provide the background resting
membrane conductance which is important
for the repolarization of the membrane.
Voltage Gated K Channels
- Each channel is 4 subunits.
- Each subunit 6 transmembrane domains.
- S4 is the voltage sensor.
- 4th transmembrane domain contains a charged motif. And this charged S4 is the
voltage sensor
- There is a pore forming segment.
- Voltage gated channels gated by transmembrane potential. They open by
depolarization. Some inactivate. Slower than Na+ channels.
How does channel allow larger K+ but not smaller
Na+?
An unusual potassium channel is isolated from V1/2 of Activation:
Streptomyces lividans. It is easier to purify. o It tells us where half of the channels are open
It is similar enough o eukaryote potassium channels. and it’s a way of measuring, describes the
They found that ther eare four highly conserved voltage sensitivity.
residues (TVGYG). o Potassium channels open and close more
One potassium ion will bind to the special region slowly than sodium channels because of the
which results in a conformational change. That is the four subunits- rate of opening is proportional to
molecule actually changed its shape. Meaning that the some value raised the power of four thus,
ion can move down and then another ion can take its taking long time.
place.
Key thing is that potassium ion does that but sodium
ion doesn’t evoke that conformational change.
, Voltage Gated Na Channels
- Each channel is 1 alpha and 1 beta subunit. Each channel has only
one protein (K has four).
- Alpha subunit is the pore-forming element (main one).
- Alpha subunit has 4 structural domains.
- Each structural domain has 6 transmembrane domains.
- S4 contains the voltage sensor.
- Accessory beta subunits alter gating properties.
- Inactivation ball.
- Intracellular sites for phosphorylation.
- Extracellular and pore sites of drugs.
- There is an area for modulation by phosphorylation. Thus, you can phosphorylate the channel and
charge its getting.
- There are sites for drugs to act either extracellularly or even within
the pore.
- Has inactivation particle (part of the molecule, not hanging).
- Na channels inactivate:
o Due to physical blocking with particle.
o The key amino acid motif IFM is required to maintain
closure of the inactivation gate.
o Cutting out IFM region-loss of inactivation.
o Adding peptide- activation.
- Na+ channels cycle through 3 states. If you depolarize the cell, that
causes opening the channel. Sodium entering is a negative current.
Same act of depolarization also causes inactivation. Thus, the
channel becomes blocked on the inside. The only way to relieve that
block is through hyperpolarization.
- You can only go into inactivated state from the open state. So, meaning that inactivation must follow
from after the open state.
Voltage-Dependent Properties of Na+ Channels
V1/2 of activation- amplitude measurement of the
inward current (in graph)
V1/2 of inactivation
3 states: open, closed, inactivated
Quantity is not important, the proportion of the dotted
points on the graphs are important.
Proportion of channels which were open to compared to
what we would get if they’re all open.
Selectivity and Voltage-
Sensing in Na+ Channels
a. One a forms tetramer-like channel
b. Pore forms funnel and selectivity filter (charge repels negative ions)
c. Arrangement of domains in 3D
d. View of selectivity filter
e. Voltage sensor- displacement of the charged S4 domain results in
conformational changes.
The action potential is mediated by ion channels.
There are many ion channels present in the membrane.
The main ones are sodium and potassium channels.
There are many other ion channels involved in neurons and
they all play a part in shaping the action potential.
Leak K Channels
- 4 transmembrane domains.
- 2 pore forming domains
- Not voltage gated. They are open all the time.
- Leak channels provide the background resting
membrane conductance which is important
for the repolarization of the membrane.
Voltage Gated K Channels
- Each channel is 4 subunits.
- Each subunit 6 transmembrane domains.
- S4 is the voltage sensor.
- 4th transmembrane domain contains a charged motif. And this charged S4 is the
voltage sensor
- There is a pore forming segment.
- Voltage gated channels gated by transmembrane potential. They open by
depolarization. Some inactivate. Slower than Na+ channels.
How does channel allow larger K+ but not smaller
Na+?
An unusual potassium channel is isolated from V1/2 of Activation:
Streptomyces lividans. It is easier to purify. o It tells us where half of the channels are open
It is similar enough o eukaryote potassium channels. and it’s a way of measuring, describes the
They found that ther eare four highly conserved voltage sensitivity.
residues (TVGYG). o Potassium channels open and close more
One potassium ion will bind to the special region slowly than sodium channels because of the
which results in a conformational change. That is the four subunits- rate of opening is proportional to
molecule actually changed its shape. Meaning that the some value raised the power of four thus,
ion can move down and then another ion can take its taking long time.
place.
Key thing is that potassium ion does that but sodium
ion doesn’t evoke that conformational change.
, Voltage Gated Na Channels
- Each channel is 1 alpha and 1 beta subunit. Each channel has only
one protein (K has four).
- Alpha subunit is the pore-forming element (main one).
- Alpha subunit has 4 structural domains.
- Each structural domain has 6 transmembrane domains.
- S4 contains the voltage sensor.
- Accessory beta subunits alter gating properties.
- Inactivation ball.
- Intracellular sites for phosphorylation.
- Extracellular and pore sites of drugs.
- There is an area for modulation by phosphorylation. Thus, you can phosphorylate the channel and
charge its getting.
- There are sites for drugs to act either extracellularly or even within
the pore.
- Has inactivation particle (part of the molecule, not hanging).
- Na channels inactivate:
o Due to physical blocking with particle.
o The key amino acid motif IFM is required to maintain
closure of the inactivation gate.
o Cutting out IFM region-loss of inactivation.
o Adding peptide- activation.
- Na+ channels cycle through 3 states. If you depolarize the cell, that
causes opening the channel. Sodium entering is a negative current.
Same act of depolarization also causes inactivation. Thus, the
channel becomes blocked on the inside. The only way to relieve that
block is through hyperpolarization.
- You can only go into inactivated state from the open state. So, meaning that inactivation must follow
from after the open state.
Voltage-Dependent Properties of Na+ Channels
V1/2 of activation- amplitude measurement of the
inward current (in graph)
V1/2 of inactivation
3 states: open, closed, inactivated
Quantity is not important, the proportion of the dotted
points on the graphs are important.
Proportion of channels which were open to compared to
what we would get if they’re all open.
Selectivity and Voltage-
Sensing in Na+ Channels
a. One a forms tetramer-like channel
b. Pore forms funnel and selectivity filter (charge repels negative ions)
c. Arrangement of domains in 3D
d. View of selectivity filter
e. Voltage sensor- displacement of the charged S4 domain results in
conformational changes.
