MT - Ion Channels Flashcards
The thalamocortical neuron has similar channel properties to the ______ in the ______.
Sa node (funny current) channels in the heart.
How many proteins are required to make a voltage-gated K+ channel? How many transmembrane domains do each of these proteins have?
Need 4 proteins, each with 6 transmembrane domains.
How many proteins are required to make an inward rectifier K+ channel? How many transmembrane domains do each of these proteins have?
Need 4 proteins, each with 2 transmembrane domains and a pore loop..
How many proteins are required to make a two pore K+ channel? How many transmembrane domains do each of these proteins have?
Need 2 proteins, each of which have 4 transmembrane domains and 2 pore loops.
Imagine a single protein from a K+ channel. Which transmembrane domain contains the voltage-sensor? What amino acids are common here.
S4. Contains many arginine residues.
Where in the body are GIRK channels found? What kind of channel are they?
They are inward rectifier K+ channels found in the heart.
What differentiates the membrane potential trace of a voltage-gated K+ channel from that of an inward rectifier K+ channel?
Vgated: rapid peak with relatively fast repolarization.
Rectifier: Slower activation but little/no repolarization.
What are the BK, IK, and SK channels (think about a specific ion/ions)?
Big (BK), intermediate (IK, and small (SK) conductance Ca2+-activated K+ channel
What toxin is capable of blocking big conductance Ca2+-activated K+ channels (BKs)(KCa1.x)?
Scorpion toxins charybdotoxin and iberiotoxin.
What channels are Scorpion toxins charybdotoxin and iberiotoxin known to block?
Big conductance Ca2+-activated K+ channels (BKs).
What toxin is capable of blocking small conductance Ca2+-activated K+ channels (SKs)(KCa2.x)?
Apamin, a component of bee venom.
What toxin is capable of blocking intermediate conductance Ca2+-activated K+ channels (IKs)(KCa3.1)?
Scorpion charybdotoxin.
How many transmembrane domains do big conductance Ca2+-activated K+ channels (BKs) have? Any pore loops?
7 (one extra!). 1 pore loop.
How many transmembrane domains do small/intermediate conductance Ca2+-activated K+ channels (SKs/IKs) have?
- 1 pore loop.
Why do bee stings hurt?
Bee venom contains aptamin. This blocks the Ca2+-activated K+ channels from repolarizing the membranes, causing perpetuated firing.
What is the K+ channel “signature sequence”? Where is it in the channel?
TVGYG. It is contained in the selectivity filter.
Each subunit in a K+ channel has _ transmembrane ______, a _______, a pore helix, and a _______ ________.
… 2 transmembrane α-helices, a turret, a pore helix, and a selectivity filter.
Are both openings of the K+ channel the same charge? What charge(s) are they?
They are both negatively charged.
How many possible locations could we find a K+ ion in the K+ channel selectivity filter?
There are 4 potential locations.
How many K+ ions are likely passing through the K+ channel filter selectivity at a given time? What else is in the channel during this time?
Only 2. 2 water molecules occupy the other 2 potential locations.
What feature of the K+ channel pore helices helps to stabilize the hydrated K+ through the channel?
They all point with their carboxyl ends towards the central cavity. This partial negative charge interacts with the cation.
How do the subunits move to open/close the K+ channel? When does this happen?
With membrane depolarization, the S4-S5 linker moves upward (closed) or downward (open), twisting the channel proteins closed/open.
How are the structures of the Na+ and Ca2+ channels similar to the K+ channels? How are they different?
They have the same general structure with 6 transmembrane domains, but instead of having these on 4 different proteins they just have one long protein with 4 of these “K+-like” 6 domain motifs. (24 TM domains total).
What toxin is known to block Na+ channels? What else?
Tetrodotoxin from pufferfish. Also lidocaine (local anesthetic) as well as phenytoin and carbamazapine (anticonvulsants).
Nav1.1-Nav1.4, Nav1.6-Nav1.7 are ____ to tetrodotoxin (TTX).
Highly sensitive (<30 nM).
Nav1.5 are ____ to tetrodotoxin (TTX).
Intermediately sensitive (2 microM).
Nav1.8 and Nav1.9 are ____ to tetrodotoxin (TTX).
Insensitive (unaffected).
How many Na+ ions will be in the Na+ channel selectivity filter at any time?
2-3.
How many pore helices per domain in a K+ channel? What about an Na+ channel? Also give the total # per channel.
K+: 1 (so 4 per channel)
Na+: 2 (so 8 per channel)
Why are K+ channels not permeable to Na+ ions, even though Na+ is slightly smaller?
K+ is dehydrated as it passes through the channel, but dehydration of Na+ is unfavourable. Hydrated Na+ is too large to fit.
Are AAs in the K+ channel charged? What about in the Na+ channel? Why?
In Na+ channels, the -vely charged AAs are needed to strip the hydration shell off the Na+ ions. No charged AAs in K+ channels.
What differentiates an α-helix from a 3₁₀ helix?
α-helix: 3.6 residues/turn
3₁₀: 3 residues/turn (they line up!)
How are 3₁₀ helices leveraged in the Na+ channel?
Contain -vely charged AAs which stabilize the Na+ ion as it passes through the membrane.
What differentiates the inactivation of K+ channels and Na+ channels?
K+: just close normally
Na+: have an inactivation gate which blocks the pore on the cytosolic side.
Where is the inactivation gate of an Na+ channel located on a diagram of topographic structure?
On the cytoplasmic loop between domains 3 an 4.
How can we determine the reversal/equilibrium potential for an Na+ current from a graph?
It’s just the x-intercept of the graph.
What are the 4/5 types of voltage-gated Ca2+ channels?
- L
- P/Q
- N
- R
- T
What toxin inhibits the N-type voltage-gated Ca2+ channels?
ω-conotoxin from that crazy underwater snail.
What toxin inhibits the P-type voltage-gated Ca2+ channels?
ω-agatoxin from the funnel web spider.
What toxins inhibit the L-type voltage-gated Ca2+ channels?
Dihydropiridines (ex: nimodipine and nifedipine)
What is the general role of HCN channels?
To act as pacemakers (produce funny currents).
How are HCN channels activated?
By hyperpolarization.
What ions do HCN channels flux?
Na+ and K+ (mostly).
What must bind to the C-terminal region of an HCN channel?
cAMP.
Which types of Ca2+ channels are involved in producing the funny current in the SA node of the heart?
T-type and L-type Ca2+ channels.
