Unit 1 Q&A
From NeuroWiki
Q) If neurons don't continue to divide, how do you get brain tumors?
A) If a cranial neuron is dividing in an adult, then it may be a tumor. The cellular mechanisms that stop cells from dividing have failed and these cells begin to divide. There are non-neural brain tumors, also. About half of the brain is composed of glial cells. These divide (and form tumors) regularly.
Q) If Acetylcholine has an inhibitory effect on the heart, and if nifedipine stops the release of acetylcholine, then why is nifedipine used as a treatment for prinzmetal angina?
A) Your original suppositions are not correct. Acetylcholine receptors come in a vast array of types. What is worse, individual receptors have opposite effects on the same cells. This gets complicated, but the heart is auto-regulated, and it is controlled by the sympathetic and parasympathetic system. The latter typically involves muscarinic receptors that "modulate" the heart – it is insufficient to say 'inhibit'. M1 and M2 receptors are the majority of those found under the control of the vagus nerve. A half dozen muscarinic receptors have been identified so far.
As to the specifics of prinzmetal angina, this is not a heart-wide affect, the constriction is in the vessel walls without an apparent external signal. Nifedipine has no specific affect on acetylcholine, it is more specific to block calcium channels. Treatment with nifedipine reduces the over-all likelihood that calcium channels will be open, low doses are sufficient to stop whatever mechanism (might be local to NMJ's) in the parasympathetic vagal neurons, or it might be specific to the smooth muscle cells in the vesels) is causing the restriction.
Q) I had a question on the potassium channels after the lowest part of the undershoot. If the potassium voltage-gated channels are slow to close and if this causes the undershoot, does the Permeability of K change once again to bring the potential out of the lowest part of the undershoot in concert with the Na / K pump?
A) Yes, the potassium channels are largely closed during the undershoot. This allows the sodium and chloride currents to return the cell to resting potential.
Q) I was wondering about the neurobiology of drinking the popular South American tea called Yerba Mate. I know the tea has some caffeine, but they (South Americans) claim that the caffeine is not what gives the tea its characteristic revitalizing effect.
A) From everything that I have seen, it has few anti-oxidants compared to green-tea. The primary stimulant is caffeine, but there may be something that has not been found yet. Never know. All scientific studies seem to point to some trace anti-glycation effects, but that would only impact folks with diabetes.
Q) What would happen if someone just sat down with a spoon and ate a bucket of salt? This would increase the outside concentrations of both Na and Cl, so doesn't seem like there would be a significant change in the resting membrane potential. On the other hand would this affect how the neuron would experience an action potential?
A) Any change in concentration of salt would change the equilibrium of salt (driving it higher) and so, also increasing the electromotive force on the Na+ when the channels open. You would reach threshold quicker and you would have a steeper activation of the action potential.
Q) You mentioned that one way to effectively stop a neuron from firing no matter what would be to hyperpolarize the axon close to the terminal end, adding chloride channels at that end, so that the voltage necessary to open the calcium channels can't be reached. Then today, that a neuron can produce channels that can open at higher or lower voltages. So in response to trying to prevent the flow of calcium, would the cell make new calcium channels that open at a lower voltage?
A) Happens all the time. Within limits.
Q) Glutamate is broken down by GAD into GABA. GABA is loaded into the vesicles and fused into the postsynaptic membrane. Then GABA attaches to the GABA receptors in the postsynaptic membrane. Do some of the GABA Neurotransmitters get re-transported randomly? Or are they specifically selected to return to the Glial cells/Presynaptic Cell?
A) Not quite sure what you mean. There is a specific re-uptake mechanism through glial cells. But the pre-synaptic cell can take up some GABA to reload into vesicles. This is all happening to change the relative concentration of GABA in the synapse. After they are retransported by GAT transporters to the Presynaptic cell, they either are broken down or they are reloaded into vesicles ready for fusion.
Q) A final question is about VIATT. Is this the channel in the vesicles that allows the loading of GABA?
A) I wouldn't call it a channel. It is a transporter that relies on facilitated diffusion and co-transport to load the vesicles.
Q) In the research says that if the inactivation gate is cut off, the voltage gated sodium channel still functions...is the shape action potential different in any way from a normal action potential?
A) Yes, it has a greater amplitude. Much closer to the equilibrium potential for sodium.
Q) After the end of the falling phase when the membrane potential dips below the equilibrium potential for potassium, the cell then depolarizes to reach its resting potential. Is that slight depolarization due to other ions or inward rectifier potassium channels or a combo of both? Also, why would most potassium channels be fast-activating, fast-inactivating? Seems like you would want more delayed rectifiers to ensure that the cell is completely reset.
A) It does not ever reach the equilibrium potential for potassium, it dips below resting potential. Mostly due to the currents of sodium and chloride. The presence of fast activating, fast inactivating channels does two things it ensures that amplitude of the action potential is fixed to a maximum amplitude and it give shape to the entire spike. The cell can constantly shift the relative numbers of delayed-rectifyers and A-type current channels (fast activating) to shape the action potential. The cell usually have many more delayed rectifiers than anything else.
Follow up: Q) So we thought that inward rectifiers allow for potassium to return into the cell, which allows the cell to return to resting potential from the undershoot. Is this true? If so, how do chloride ions leaving fit in here along with sodium currents coming in?
A) This would be true if the membrane were more negative than the potassium equilibrium potential. The undershoot typically is not (for the whole cell). However, just to confuse you a little– locally, the membrane is actually more negative than the potassium equilibrium potential. Inward rectifiers are a rare breed. You can all but ignore them at the moment.
Q) Also, how do chloride ions fit into the big picture? In a study group you stated that chloride is largely responsible for bringing the cell back to the resting potential and that it's 10x more permeable than sodium, however it's also been stated that potassium serves this same function. We know that GABA and Glycine open chloride channels, but what happens then? What is the effect of chloride working with these neurotransmitters?
A) If the potassium currents are greatly reduced, then only chloride and sodium currents are left. Therefore, since chloride has 10X the permeability of sodium it serves to bring the potential back to rest.
Q) There's specific alpha and beta versions of adrenergic receptors, different acetylcholine receptros (M1-M5), dopamine receptors, and serotonin receptors. Do we have to memorize all these different types of receptors, what they act on, their specific G protein pathways, or just understand that there's a large variety of different receptors for each?
A) Hmm, I would focus on: First knowing the differences between alpha and beta adrenergic receptors. I would then memorize where the alphas and betas are expressed.... Then I would note that I showed a few slides that specifically mention adrenergic receptors and the G proteins coupled with those receptors.
Then I would look at which muscarinic receptors work with Gq proteins. And finally what affect the heart.
You can ignore serotonin, histamine and dopaminergic receptors until Unit 3.
Q) Why do there exist benzodiazepene binding sites in our bodies? What I'm asking is what is it substituting as an agonist.
A) We don't know. Many drugs and toxins (the drugs are often designed because of the toxins) that bind to receptor sites that seem to have no endogenous agents acting at that site. Proteins are apt to bind to many things, many toxins/drugs bind to seeming unimportant domains. But their importance is discovered after the toxin is found.
Q) I was wondering whether adrenergic receptors were regarded as the same thing as norepinephrine/epinephrine receptors
A) Yes.
Q) Could I make sure I have this correct? Excess potassium in the blood will be deadly because that would increase the resting potential of the cells. Without a negative resting potential, the sodium will not have as strong influx when sodium channels are opened, so the cell is less likely to generate an action potential.
A) All correct.
Q) When do we have LTD and LTP. What causes them?
A) These are two processes, not discrete events. Think of it this way: LTP is a way of making communication between two cells stronger, and LTD is the reverse. In the brain, different synapses have different degrees of "fidelity", or likelihood that a signal will be passed from one cell to another. As the brain develops and changes throughout your life, the primary mode of this change is at the synapse. LTP and LTD are ways to change how neurons talk to one another. This is believed to be a basic component of learning.
Q1) Is there anything else you can do to change the width of the action potential? A) many things. Q2) So, do all of these things lead up to an increase in the speed of potassium leaving the cell during repolarization, or is there specifically something else you could do: for example, increasing the speed of sodium leaving the cell during depolarization? A2) Hmmm, sodium does not leave the cell during depolarisation, it enters. You can change: the concentration of ions, the number of channels open, the types of channels present altering conductance and their gating. You can change other ions permeabilities, and change the individual gating on channels.
Q3) Are the implications for the axon that there is an increase in the number of potassium channels? A3) Yes. It affects the refractory period. Q4) Is the refractory period shortened by the increase of voltage gated potassium channels or is it only affected by the inward rectifiers? A4) Yes, voltage-gated potassium channels.
Q5) Also, what can you do to change the amplitute of the action potential? A5) Affect the sodium current, for starters. Q6) So for example, if you increased the amount of sodium (or NaCl) outside the cell, this would raise the equilibrium potential for sodium and the amplitude would increase? A6) Yes, or have the current stay open longer.
Q7) Oh, and one more question. How is the voltage value of the reversal potential between Na and K not halfway between? Is it because the receptor protein through which Na and K flows is bound by ACh, which is concentration dependent, and that has some sort of affect on which equilibrium potential (Na or K) the reversal potential is closer to? I'm just really confused about that whole thing. A7) Have one ion conduct at a faster rate than the other. This will drive the reversal potential closer to that ion's equalibrium potential.
Q1) Are neurotransmitters specific to a given neuron (for example, are there neurons that only release glutamate)? Or can any (or most) neurons release one or more different neurotransmitters? If so, how does the neurotransmitter distringuish between the transmitters if the signal at the the end of the axon is the same (a non-gaded action potential)? A1) Generally, the rule will be one neuron produces and releases one neurotransmitter. There are exceptions, but none that we are concerned with at the moment.
Q2a) For a given neuron, if we assume the relative concentrations (in/out) are: Na: 12/120, K: 140/5, and Cl: 15/120, what would be the change in these concentrations during and after an action potential? A2a) The change would be so small that it is essentially unmeasurable. So, we are assuming that there is *no* change in concentration as a result of an action potential.
Q2b) Specific numbers obviously mean nothing, but an idea of how much of these ions rush in/out would be good to know. A2b) Zilch (technical term)
Q2c) Furthermore, is a new resting potential established after an action potential? Or are the concentrations fully resolved back to their original state? Q2c) Fully resolved to within measurable tolerances.
Q2d) I guess my underlying question is whether the leak channels are enough to compensate for the increase in Na inside the cell and the decrease of K inside the cell. A2d) Yes.
Q3) How is blood pressure related to the concentration of the various ions inside/outside the cell? People with high blood pressure are generally advised to lower sodium intake... Would an increase in clorine or potassium lower blood pressure? A3) Higher blood pressure can mean (but not always) an increase in blood volume. This can mean an increase in water volume and a commensurate drop in ion concentration. The body uses the kidneys (and, to some extent, the gut) to regulate salt levels in blood serum. Poorly functioning kidneys can lead to heart/neurological problems. Chlorine generally follows sodium. A drop in sodium levels means a similar drop in chlorine levels (unless you are substituting KCl in your diet). Less salt, less water, less blood volume, less pressure. Poking holes in the circulatory system works too, but is not advised.
Q) What is the importance of APV in LTP? A) None that I know about. But you might consider that APV is an NMDA receptor antagonist. This could be used to determine the receptors involved in LTP....
Q) In class we discussed that at low Ca levels, a cell goes through LTP and at high Ca levels, a cell goes through LTD. This makes sense in the diagrams, but on wikipedia it says that many scientists proposed ....LTD at low calcium levels and LTP at high calcium levels. A) These are two proposed processes that are involved in the synaptic plasticity found in learning circuits. Essentially, there is no definitive answer yet.
Q1) H/Glu antiport can be affected by metabolic or respiratory acidosis? A1) Metabolic at the cellular level, yes. Q2) Is H/Glu in the VGLU? That seems to be an obvious question. juat to make sure A2) The VGLUT is a proton-glutamate anti-port.
Q) Guessing there are many many many channels on a single cell. After a G-protein pathway is activated, is the ensuing phosphorylation specific to one target (say, just one type of K channel), or is it more like laying down a carpet of phosphorylation across anything phosphorylatable? A) It is believed to be a pathway with at least some specificity. There is likely to be some "slop" though. In general, PKC is targeting a specific channel with the help of another protein.
Q) In an earlier question, you answered that an increase in voltage gated K channels would decrease the refractory period. I thought that an increase in K channels would cause the undershoot to be greater because more K would rush in. Wouldn't this increase the refractory period because it takes longer for it to come back to resting potential? A) The slope of repolarisation would be much steeper. The cell will return to rest much more quickly. The refractory period ends when the undershoot is achieved, so getting there quicker will shorten the period.
Q) Is the concentration gradient due to the fact that ions are charged so would want to be further from same ions with a like charge? Or would there be a concentration gradient driving things into or out of the cell even if they were uncharged? Guess I'm asking if the repulsion between same ions is part of concentration gradient or electrical gradient. A) The repulsion between the same species of anything is the basis of a concentration gradient. The "force" involved is entropy. Any disparate distribution implies an loss of entropy, which goes against thermodynamic trends. In a closed system like a membrane, the lack of direct energy driving the ions into higher concentration is countered by entropy.
Q) Is threshold an innate property of that voltage gated Na+ channel or can it be changed? If it can be changed, how can you change it? A) To some degree, yes. You can change threshold for the cell by changing which sodium channels are in the membrane. There are also other sub-units that affect the channels. These can be expressed to change the kinetics of the channels.
Q1) I was wondering about the classifications of some ion channels. Are voltage-gated ion channels considered ionotropic? In my notes, I have that ligand-gated ion channels are ionotropic? Are both ionotropic or just the ligand-gated channels? A) Anything that passes ions across the membrane is ionotropic.
Q2 )I thought I remebered you mentioning that ligand-gated ion channels usually have a much slower conductance than voltage-gated ion channels. Is this correct? A2) Umm, as a general rule, yes. But we can get into trouble with too many such generalizations.
Q3) With regard to reversal potentials, how are they calculated if you have more than one ion in solution? A3) This would not likely be a case of calculation (although it is possible), it is more derived from voltage clamp data.
Q4a) Capacitance is nearly the same as a radial current, correct? By this, I mean the capacitance (Bad) is lowering the conductance in an unmyelinated axon because the electrical gradient is pulling the (+) ions towards the negative outside? Q4b) That might not have made sense. I am confused b/c I know that capacitance (in a resting neuron) is the ability of the positive ions outside to pull the negative ions inside towards the membrane. When the neuron receives an action potential, is the capacitance the Sodium ions leaving through channels? A4a) Capacitance generates radial (non-axial) currents. The negative charges are *inside* the cell. A4b) During an action potential, capacitance draws ions away from the axial current.
Q5) In the review, towards the end you said a big question on the test would come from this. "apply your knowledge of what must be true of axons for them to propogate signals through changes". Is this just asking if we know that axons can change the "makeup" of channels, etc in their plasma membranes due to specific neurotransmitter release? A5) Hmmm, I want you to think of all the ways that you can change an axon to accommodate changes that may have occurred due to other factors. This includes *everything* from channels, receptors, signaling pathways, capacitance, to Nodes of Ranvier, and and and...
