L18 - Voltage gated ion channels Flashcards
structure of VGIC
Formed by one alpha-subunit that
is a contiguous polypeptide with
four repeats
OR
4 alpha-subunits each with a single domain
Each domain has 6 alpha helical
transmembrane segments
* The fourth transmembrane
segment contains a voltage
sensor
voltage sensors
detects the electric field/movement of
charge in the membrane adjacent
to the ion channel
a conformational change will occur once threshold is reached, opening the channel
VGIC and action potential
Action potentials are initiated,
maintained and “turned off” due to
the activation of different voltage
gated ion channels
what is Nav
Sodium VGIC
function of Nav in action potential
Activation of NaV initiates the
action potential and is responsible
for the depolarisation phase of the
action potential
speed of Nav
Close ~1-2ms within opening
known as fast inactivation
where are action potentials generated
the axon
which Nav subtypes are located on the axon
Nav 1.6 and Nav 1.2
Nav 1.6 function
primarily responsible for the “forwards propagating action potential”
Nav 1.2 function
primarily responsible for the “backwards propagating action potential”
Nav drug targets
Local anaesthetics bind to a receptor site lining the inside of the pore, which when occupied, blocks the pore
Many animal toxins (e.g., TTX) potent toxins for Nav and physically block the Nav pore
what is a Kv
potassium VGIC
function of Kv
Responsible for the repolarisation and hyperpolarisation of the action potential
Regulate the frequency at which
action potentials can be
generated (firing frequency)
Help set the “resting” membrane potential
how many families of Kv are there
12
Kv drug targets
Modulators block the pore
from the external or internal side,
or by modifying the voltage sensor
- Metal ions
- Organic small molecules (200- 500Da)
- Venom peptides (3-6 kDa)
Kv inhibitors treat
depression, MS, cognition disorders
Kv activators treat
ADHD, seizures, pain, CNS hyperexcitability
what is Cav
calcium VGIC
Cav function
important for regulating the potential
of the membrane. Action potential
frequency and for signalling
pathways
how many families of Cav are there and what their functional categories
3 - high voltage and low voltage activated
Cav drug targets
Cav channel blockers most aim to
alter the excitability of neurons by
changing the amount of membrane depolarisation and regulating the firing frequency of neurons
