Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
34 Cards in this Set
- Front
- Back
|
What are the 4 types of ion channels?
|
Voltage-gated; ligand-gated; mechanosensitive; thermosensitive
|
|
|
What architecture do most ion channels share?
|
They have a barrel stave; could be tetrameric, pentameric, etc. There's a pore that goes down the middle. The save is made up usually of independent units. The subunit folds up on itself.
|
|
|
What's different about architecture of a voltage-gated Cl- channel?
|
Homodimeric, and pores do are not along the axis of symmetry.
|
|
|
What's the major ion channel function?
|
Permeation. They permeate ion of choice and do it very fast; it goes down the electrochemical gradient from high to low, then let it go v. quickly. If you love me, let me go (and know).
|
|
|
How do ions flow through channel?
|
They flow bidirectionally depending on the electrochemical gradient. The channel is very selective.
|
|
|
How do ions achieve a rapid rate of permeation and also stay selective?
|
Imagine your pore has 4 binding site, and it binds the same ion, so the same charge. You bind your first one; has a v. high affinity. You bind your seond one. Affinity is a little lower b/c of charge:charge repulsion. Ions hop from site to site, either in or out, depending on electrochemical gradient
|
|
|
How can an ion channel be selective for K+?
|
Na+ and K+ are equally hydrated in water, but Na likes water a little better. In K+ pore, the carbonyl oxygens in the pore would come in and provide K+ binding sites, while Na+ would rattle around. Na+ would rather be in water than K+, and K+ wouldn't know difference between water. Na+ would rather stay in water than go down the pore, b/c it's more energetically favorable.
|
|
|
Other than permeation, what's a major ion channel function?
|
Gating. Just means opening and closing.
|
|
|
What are characteristics of voltage-gating?
|
Tetrameric. 6 transmembrane proteins. Typically closed @ resting membrane potential of cell. Opens @ membrane depolarization.
|
|
|
What are voltage-gated channels used most for?
|
The repolarization of action potentials in the nerve, muscle, and heart.
|
|
|
Tell me about the S4 domain of the voltage sensor?
|
It's + charged. Pulls open the gate. Enough hydrogen bonding that we don't . . . Reem?
|
|
|
What does a voltage sensor do?
|
It can sense changes across the membrane and yank the gate open. Makes structural changes in response to voltage changes.
|
|
|
How/why does a voltage sensor bring up the gate?
|
Depends on depolarization. As the cell membrane becomes more +, the positively charged voltage sensor jumps outward (away), and end up opening the gate. It's just trying to get away from the + charge.
|
|
|
What is inactivation gating?
|
Exactly that. Inactivating the channel.
|
|
|
What model do we know most about wrt inactivation gating? How does it work.
|
The ball and chain model. Ball loops up and plugs the channel. Experiments done where we've cut off the ball, and channel stays open.
|
|
|
What, most importantly, does inactivation enable the voltage-gated channels to do?
|
It allows them to close when they would otherwise be open (that is, voltage is @ right # for them to be open, but we want them closed, so we just plug them up with ball and inactivate them.
|
|
|
What's an inward rectifier?
|
A leak channel that's only open @ negative voltages.
|
|
|
How do we plug up an inward rectifier?
|
Stuff some polyamines and Mg2+ to bind to inner vestibule and prevent K+ from leaking out.
|
|
|
What about QT time in electrocardiograms? How can K+ conductance mess with that?
|
We need K+ (and their channels) to go back to rest. If there are mutations in the channels, we can get a longer QT time --> can lead to arrythmias and death.
|
|
|
What is HERG?
|
A protein in the cytoplasmic vestibule of K+ channels. It binds hydrophobic amines very well (generally binds small, h-phobic, + molecules well).
|
|
|
What was the deal with HERG and Seldane?
|
Seldane inhibit HERG. Would get trapped in cardiac channels and pts would get arrythmias. All drugs now tested for Herg binding. Seldane was + charged, which the channels like.
|
|
|
What about allegra and seldane?
|
Allegra is the active part of Seldane. It's negatively charged, so the channel isn't interested.
|
|
|
What is the Acetylcholine Receptor (AChR)?
|
Ligand-gated; cation-selective channel founds in neurons and skeletal muscle.
|
|
|
What activates AChR?
|
Acetylcholine and nicotine.
|
|
|
What's its main function?
|
Plays key role in fast synaptic transmission @ neuronal and NMJ. AcH is a NT.
|
|
|
How does inactivation of channel basically work? Just an outline.
|
You have a closed channel. Add ligand. It opens. Ligand sticks around too long and so channel closes. Then it becomes desensitizes to the ligand.
|
|
|
What does nicotine do to AchR? How?
|
It desensitizes AchR to nicotine. Nicotine in + charged. It binds and stays bound for so long it inactivates the channels.
|
|
|
Why is a cigarette in the morning taste the best?
|
B/c smokers upregulate production of AchR, so when you light up in the a.m., you've got all these new receptors @ the synapse. Feels good!
|
|
|
What is slow channel syndrome?
|
A congenital syndrome where the AchR stays open for too long.
|
|
|
Why does it happen?
|
There are mutations in the AChR binding domain that increases affinity for Ach (remember, if you love something, let it go). It holds on too long, and you get channel activity for prolonged bursts.
|
|
|
What is TRPV1: The Capsaicin Receptor
|
It's a voltage-gated, temp-dependent channel. Cation selective. Opens and closes due to temperature. If you add chili pepper, it opens up. If you add menthol, the cold channel opens. Wasabi works here. The more pungent a pepper, the more TRPV1 is activated.
|
|
|
Evidence suggest that following an injury, neuropathic pain sticks around b/c:
|
Nociceptive sensory fibers become hyperactive, are constantly shooting pain to the stimuli even when there are no noxious stimuli present.
|
|
|
What is relationship between TRPV1, nociceptors, and pain?
|
Nociceptors have TRPV1, which initiate APs to the spinal cord. But the sustained activation of TRPV1 --> increased intracell Ca2+ --> cessation of pain for awhile (though reversible)
|
|
|
How does what we know about TRPV1, nociceptors, and pain lead to possible treatment?
|
Clinical studies have shown that applying capsaicin-infused cream to skin for a few weeks results in a cessation of. Many don't want to do this b/c it hurts like hell.
|
