Term
| Do ion channels bind to the solutes to be transmitted? What sits in ion channels? |
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Definition
| They do not bind the ions. Water is usually sitting in the channel. |
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Term
| How do channels open/close (in a general sense)? |
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Definition
| They undergo conformational changes as a result of signal transduction. |
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Term
| When channels are open, what happens? What is amazing about ion channels? |
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Definition
| When channels open, all the ions can flow in a fast rate. What's amazing is that somehow the channels are selective usually for ONE type of ion! |
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Term
| What are the two main types of voltage gated ion channels? |
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Definition
| inward rectifiers and voltage-gated ion channels |
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Term
| How many pieces are in an inward rectifier K+ channel? What is the approximate shape? |
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Definition
| These are tetramers (4 pieces, dumbass) and they are in an "inward teepee" sorta shape. |
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Term
| What is at the extracellular side of the inward rectifier K+ channel? |
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Definition
| There is a p loop which is really teeny and narrow. This is where the...p...otassium slides in. But only potassium can fit in there. Perfect fit. lol |
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Term
| Talk about the selectivity filter of the p loop. |
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Definition
| Well, there are electronegative oxygens that line the inside of it. The electronegativity of the oxygen attracts it to K+. The perfect match of the K+ with the oxygens somehow makes it more favorable for the K+ to bind that than water. So, only K+ comes through (no water), and K+ only goes through in a single file line. Na+ cannot bind the oxygens (carbonyls) in the right way, so it can't loose its water and thus can't come through. |
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Term
| How can the inward rectifier K+ be blocked? What does this do to the conductance? |
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Definition
| on the cytoplasmic side, certain stuff can bind to acidic residues, and block the channel. This messes up conductance and makes conductance quite low. (and resistance quite high). Mg+ is an example of what can do this. Also, polyamines like spermine. |
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Term
| Why are K+ movements outward under normal physiologic conditions? Answer this in mathematical terms using Vm and Vk |
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Definition
| Well, the driving force is outward because the Vm is more positive than the Vk (at equilibrium). So Vm-Vk = something positive. |
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Term
| If you open ion channels, and K+ is rushing out of the cell, can any K+ ever go back the other way, into the cell? |
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Definition
| Yes, this happens sometimes. |
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Term
| Why might you have backward flow of K+ ions? |
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Definition
| This is rare. Especially uncommon when the cell is highly depolarized. However, it happens more common when Vm is close to the Vk. (ie close to equilibrium) |
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Term
| What happens when a K+ comes into an inward rectifier? When would this event be common? |
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Definition
| The K+ can kick the blocking Mg+ or spermine out, and then the conductance of the channel will be very high until another blocking cation binds cytoplasmically. A well polarized membrane would be more likely for this event to happen. |
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Term
| Why are these channels called inward rectifiers? |
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Definition
Rectifiers are electrical devices that permit current to travel in only one direction. This name was
applied to the Kir channels because, under experimental conditions, they were shown to carry large
inward currents much better than large outward currents. However, the name can be somewhat
confusing, because under physiological conditions K+ currents are always outward. In excitable cells,
inward rectifiers often provide an outward current to keep the membrane polarized under resting
conditions, but shut down upon strong depolarization so as not to resist the action potentials that are
essential for the function of many excitable cells. |
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Term
| How do Kir channels (inward rectifiers) differ? |
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Definition
differ with respect to the extent that they discriminate against large outward currents.
Strong rectifiers may become almost completely blocked when Vm is more than a few millivolts positive
to Vm, whereas weak rectifiers retain substantial conductance at depolarized potentials.
SO, this way they work to keep the membrane potential that the cell is working so hard to achieve. (and spending alot of ATP on!) |
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Term
| So upon membrane depolarization, what do inward rectifiers do? |
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Definition
| They close essentially on depolarization. So, as lots of K+ gets pumped into the cell, the Kir channels close. |
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Term
| Upon membrane depolarization, what do voltage gated ion channels do? |
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Definition
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Term
| What is the structure of voltage gated K+ channels? |
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Definition
Very similar to inward rectifiers. Inward teepee of tetramer with p-loop and characteristic K+ channel sequence in the selectivity filter. The subunits are bigger than in inward rectifiers though (these have six TM helices).
Like in Kir, the p loop is on the extracellular side. |
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Term
| What contains the voltage sensor in voltage gated K+ channels? How does this work? |
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Definition
| the S4 helices have + residues. When Vm is well polarized (ie when the K+ in the cell is not that much--the cell is more negative), the channel is closed because the + residues are attracted to the negative charges in the cytoplasm (they like fold in). When the cell gets lots of positive charge (depolarized by influx of K+), the channels open and let the K+ rush out. |
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Term
| In order for the activation gate to fully open, what must happen? |
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Definition
| All 4 of the S4 helices must move to the outer position due to a lack of negative charge to be attracted to in the cytoplasm. When ALL 4 have opened, another activation gate is opened and K+ rushes out. |
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Term
| How long do K+ voltage gated channels stay open? |
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Definition
| Some will stay open until depolarization is done with. Others will just like become inactivated. |
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Term
| Explain the concept of voltage gated K+ channel inactivation. |
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Definition
voltage-gated K+ channels carry their own intracellular blocking
cations, in the form of acidic amino acids at the N-terminus of each subunit (the “ball-and-chain”)
When the activation gate opens, binding sites for the positively charged ball can lodge in the pore, and
prevent ion flow. This inactivation gate opens only upon membrane repolarization. |
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Term
| How are voltage gated Ca2+ and Na+ channels different from K+ voltage gated channels structurally? |
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Definition
The main difference is that the Ca2+ and Na+ channels are made of a single protein (not a tetramer). The protein has 4 domains which act in the same way as the tetramer does, but they are all in like one piece.
They have p loops which define their selectivity too, but they aren't as well understood. |
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Term
| How are Ca2+ and Na+ voltage gated channels closed? |
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Definition
| Positive charges just cause the thing to close on the pore. There is no ball and chain thing like with K+ |
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Term
| Where does NaCl get absorbed in the kidney? |
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Definition
The thick ascending limb of the loop of henle. Apical (lumen) transporters use the entry of one Na+ ion to
drive the uptake of two Cl- ions and one K+ ion. The basal membrane, facing the interstitial fluid,
expresses the Cl- channel. |
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Term
| What is Bartter's disease? |
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Definition
Loss of function mutation in the channels which absorb NaCl from the thick ascending limb of the loop of Henle.
Normally, the Cl- that is taken up by NKCC2 traverses the epithelial cell and exits into
interstitial space through the ClC-Kb channels (the reabsorbed Na+ is pumped out by Na+/K+ ATPase,
also located in the basal membrane). If ClC-Kb is defective, the accumulation of Cl- in the cell makes
NKCC2 operation increasingly unfavorable. Also, since that the lumenal concentration of K+ is much
lower than Na+ or Cl- and therefore rate-limiting for NKCC2 operation, the recycling of K+ into the lumen
by ROMK channels is essential for maintaining the reabsorption of Na+ and Cl-. |
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