4 - K+ Channels Flashcards
Most voltage-dependent ion channels have a ____ structure.
Most voltage-dependent ion channels have a tetrameric structure.
- 4- fold (4-domains) symmetric structure each with 6 TMD’s linked together via a “linker”
- Domains have a fixed composition and cannot ‘mix’
What is the structure of a K+ channel?
K+ channel genes usually encode only one 6TM domain, so four proteins assemble to form the ion channel
- results in diverse channel functions depending on which subunits assemble
What are three sources of variability of K+ channel function?
- Subunits may come from different genes (heteromeric channels)
- Alternative splice
- different proteins arising from the same genes
- Assembly with modifying subunits (‘accessory subunits’ ; ‘auxiliary’ subunits ; beta subunits)
What are 3 ‘Single’ Action Potential Effects of K+ channels?
- Set resting membrane potential
-influences which stimulus is needed for neuron to fire (sensitivity) - Influence AP shape
-broad AP controlled by K+ channel - Repolarize/hyperpolarize membrane
What is the subunit composition of voltage-gated K+ channels? (how many subunits, what arrangement?)
Four-fold (ie four domain) symmetric structure each with 6 membrane spanning regions
K+ channel genes usually encode only one 6TMD so four proteins assemble to form the ion channel = heteromeric channel = great diversity
Modifying subunits include: accessory subunits, auxiliary subunits, beta subunits
Differences between voltage-gated K+ channels vs Voltage-gated Na+ or Ca++ channels (selectivity, subunit arrangement)
Voltage-gated Na+ and Ca++ channels have a tetrameric structure with 4 homologous domains (I, II, III, IV) each with 6 membrane spanning regions. The domains are linked together with a “linker”
These domains have a fixed composition
What is the definition of a delayed rectifier? (why delayed? Why rectifier?)
- Delayed: channels have a delayed sigmoidal opening
- because these channels have many ‘pre-open’
states to go through before opening (all
subunits must be activated for pore to open)
2.Rectifier: K+ channels preferentially conduct ions OUT of the cell
- 2 reasons
- **intrinsic voltage dependence **Their activity depends on voltage - at neg voltages = mostly closed = low conductance
- **concentration gradient **
- K+ ions have a much higher concentration inside the cell relative to outside so at all physiological voltages, K+ ions tend to move out of the cell
Rectifier: K+ channels preferentially conduct ions OUT of the cell
-2 reasons:
Rectifier: K+ channels preferentially conduct ions OUT of the cell
2 reasons:
1. Their activity depends on voltage -
at neg voltages = mostly closed =
low conductance
2. Concentration gradient: K+ ion
have a much higher concentration
inside the cell relative to outside so
at all physiological voltages, K+
ions tend to move out of the cell**
What is a conductance-voltage relationship? What does it describe?
describes the conductance of a channel dependent of various voltages
What controls activity of M- channels?
closed by?
activated by?
M-channels are closed by the muscarinic action of acetylcholine (ACh)
M-channels are activated (slowly) by depolarization
What does closure of M-channel cause?
depolarization and suppression of the mechanism which limits repetitive discharge
- ACh is strongly excitatory in the CNS
- depolarization
- Enhanced repetitive discharge
- Increased excitability
M-channels require ____ to active
M-channels require PIP2 to active
– cleaving pip2 shuts down the channel
ACh binding to M-channel cleaves PIP2
____ is a first-in-class potassium channel opener
*
Non-selective activator of neuronal _____ channels
Retigabine is a first-in-class potassium channel opener
Non-selective activator of neuronal* KCNQ(2-5) (encode M-channels in NS)* channels
What happens to RMP when M-channels are inhibited by ACh? How does this effect AP?
RMP is higher because M-channels typically contribute to RMP
Neuron is hyperexcitable = bursting pattern (repetitive firing)
What controls activity of BK channels? What underlies Ca++ sensitivity?
A
BK channels depend on both depolarization and internal [Ca++]
Ca++ sensing mechanism is intrinsic to the channel (encoded by channel gene) ie intracellular Ca++ sensing domain
