6 - VGIC Flashcards
The a subunit of VGICs can function on their own
True
What is the role of the b subunits of VGIC
Modulate the function of the alpha subunits
What are some of the actions of the b subunit (2)
Regulate expression levels, location and trafficking
Alter voltage dependence of activation or inactivation
What can bind to the b subunit
Drugs to module function
What does phosphorylation of the b subunit do
Regulate VGIC function
What controls the selectivity of VGICs for Na/K/Ca
Aqueous pore
How do VGICs open
Contain a voltage sensor which moves in response to changes in membrane potential
Regulatory domains in related channels can regulate opening of channels true or false
True, Ca activated K channels
What is deactivation
When the membrane potential reverses back to its resting state the channel may close
What is inactivation
Voltage dependent Na channels will close immediately after being activated even when there is still depolarisation
What is the Ball and Chain model for inactivation
Influx of +ve charge will cause an intracellular domain to swing into the open pore of the channel to prevent ion flow
What does phosphorylation of VGICs do
Alter channel properties such that it responds in a different manner to allow the cell to respond to different physiological stimuli - allows for rapid changes in channel function
What are two examples of phosphorylation of VGICs
1) Protein Kinase c causes phosphorylation of a single residue in the a subunit of a Nav to slow the rate of channel inactivation
2) Phosphorylation by Protein Kinase A slows the rate of Cav channel activation and shifts voltage depndence so that it is activated at more negative potentials
What are 3 parts of Nav(1.2)
Pore region
Voltage sensors
Linker between voltage sensor and pore
What would result from blocking all Nav channels
Complete loss of sensory system
Sedations
Coma
How do many Nav blocking drugs gain access to the channel
Binding to the open state of the pore i.e. only active neurones
How many main types of Na+ channel a subunits are there
9
What do tetrodotoxins do
Bind to the external surface of the a subunit of the channel in the S5-S6 loop region and block the pore
What are two drugs that modulate Nav activity
Phenytoin and carbamazepine
What are phenytoin and carbamazepine used for
Treatment of epilepsy
Prevents seizure
How do phenytoin and carbamazepine work
Slow the recovery from the inactivated state
Limits the firing rates of neurones
What are 3 LAs
Cocaine
Lidocaine
Procaine
How do LAs work
Bind to the Na+ channel at sites exposed to the lipid membrane to block the channel
Causes Na+ to bind to the inactivated state of the channel creating a use dependent blocke
What do Kv channels do (3)
1) Set the cells resting membrane potential
2) Repolarise the cell after an action potential
3) Controlling the cell’s rate of firing and shape of the action potential
What are the two types of K channels
6 TM K channels
2 TM K channels
What do delayed rectifiers do
Delay activation after depolarisation and inactivate slowly - facilitate repolarisation
What do A-type channels do
Transiently activate when a cell is depolarised after a period of hyperpolarisation - decreases firing frequency
What do Ca-activated K channels so
Respond to Ca, remain open for prolonged period
Prolong hyperpolaisation
What do inward rectifiers do
G-proteins that can regulate their activity (GIRKs)
How does noradrenaline increase the firing activity of hippocampul pyramidal neurones
NA binds to B-adrenergic receptor which stimulates cAMP production and PKA activity
PKA phosphorylates Ca activated K channels and blocks their activity
Hyperpolarisation is reduced and neuron is kept in excitable state allowing more firing
Are many K channel blockers used to treat neurological disorders
No despite a wide variety
What is a useful K inhibitor research tool
Tetraethylamonium
What inhibits delayed rectifiers
Cs
What can Ca entry into cells trigger (6)
1) Muscle contraction
2) Neurotransmitter release
3) Activation of second messenger systems
4) Alteration in gene expression
5) Apoptosis
6) Depolarisation - Ca2+ spikes
Where are L-type Ca channels found
Cell body
Proximal dendrite
Where are Ca1.1 found
Skeletal muscle
Where are Ca1.2 found
Cardiac muscle, smooth muscle, brain
What do PQNR channels do
Regulate neurotransmitter release. Ca2+ influx through these channels causes release of NT
What is a potential treatment for chronic pain
Synthetic peptide blocker of N-type channels
What do T-channels mediate
Repetitive firing of neurones
What is the MOA for Gabapentin and pregabalin
Bind to a2d subunit to disrupt trafficking of the channel to the membrane
Selective for CaV2.2 that regulate neurotransmitter release in sensory neurones
What do cone snail toxins contain to modulate VGICs
Peptides to target ion channels, receptors and transporters involved in neurotransmission
