Voltage-Gated Ion Channels Flashcards
2 subunit types of VG Na channels
alpha and beta
Alpha subunit of VG Na channel
Modeled as 4 internal repeats
Voltage sensor of VG Na channel
TM4 (S4)
What part forms the channel of VG Na channel?
P loop, H5 or SS1-SS2
VG Na channel inactivation gate is located between?
Repeat III and IV
Activation of VG Na channel is dependent on?
Voltage (requires adequate depolarization)
Open probability of VG Na channel is dependent on?
Time (rapid inactivation)
How long does it take for VG Na channel to go from active to inactive?
1 ms
Inactivated state of VG Na channel is dependent on?
Time and voltage → requires time at negative (hyperpolarized) potential to de-inactivate
VG Na channel is blocked by?
- Local anesthetics (ex: lidocaine)
2. Tetrodotoxin
If the membrane does not repolarize, what happens to VG Na channel?
Remains inactivated for extended time
Mechanism of VG Na channel inactivation gate is called?
Hinged lid
Cytoplasm loop of VG Na channel (hinged lid) is made of?
- Isoleucine
- Phenylalanine
- Methionine
In a cell with mutated VG Na channel which remains open, what happens to membrane potential?
Stays near E(Na)
HYPP stands for?
Hyperkalemic Periodic Paralysis
Hyperkalemia means?
High blood potassium
HYPP is caused by?
Defect in sodium channels → high blood K is secondary
What is the defect in Na channels in HYPP?
Rapid deactivation → no refractory period
K channels are sensitive to?
Voltage and Calcium
T of VG K channels determines?
Tetramerization → family specific
Has phosphorylation sites
Inactivation latch of VG K channels is located?
Between loops 4 and 5
Functional characteristics (activation, open probability and inactivation) of VG K channel are the same as?
VG Na channel
VG K channels are blocked by?
- Antiarrhythmics
- Toxins
- Dendrotoxin
- Charybdotoxin
- Agitoxin
VG K channel inactivation latch is called?
Ball and chain
Which inactivation method is more rapid, hinged lid or ball and chain?
Hinged lid
Why is ball and chain inactivation slower than hinged lid?
Longer chain (chain length varies among K channels)
Activated K channel has what effect on membrane potential?
Decreases membrane potential
If drug blocks K channel, what happens to cell?
Will depolarize and have decreased ability to repolarize
Action potential comes from?
Changing conductances over time
Resting membrane potential is regulated by?
Basal conductances
What induces depolarization to threshold?
Agonist
Agonist-induced anion channels do what?
Reduce depolarizing impact of stimulating neurotransmitters (prevents reaching threshold)
V-sensitive Ca channels are important for action potential in what cels?
Cardiac and nerve
What type of channel is important for excitation-secretion coupling?
V-sensitive Ca channels
V-sensitive Ca channels have intracellular regulation by?
- Kinases
- Ca
- G-proteins
Inactivation timer of V-sensitive Ca channels
TM6 of repeat I
Voltage sensor of V-sensitive Ca channels
TM4
Subunit types of Ca(V) channels
- Alpba
- Beta
- Gamma
- Delta
Ca(V) channel functional characteristics
same as others
Ca(v)1.x is what type?
L-type (long)
Ca(V)1.x modulated by?
Dihydropyridines
Dihydropyridines are a target for?
Drug interference with cardiac modulation
Ca(V)2.x is what type?
P/N/R-type (neither)
Ca(V)2.x is found in?
Dorsal root ganglion (pain interaction)
Ca(V)2.x is blocked by?
- Agatoxin
- Conotoxins
- SNX-482
Ca(V)3.x is what type?
T-type (transient)
Ca(V)3.x is found in?
CNS (anticonvulsant target)
Ca(V)3.x is blocked by?
Kurtoxin (from scorpion)
Antiarrhythmic drugs target?
Rapidly activating cardiac K channels