Term
| 10 steps between the arrival of an action potential & a postsynaptic potential |
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Definition
1. action potential
2. nerve terminal depolarization
3. activation of voltage-gated calcium channels
4. calcium enters down a strong gradient
5. calcium triggers transmitter release
6. exocytosis of neurotransmitter
7. transmitter crosses synaptic cleft
8. transmitter binds to receptor
9. postsynaptic conductance change
10. action potential |
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Term
| What allows for the activation of voltage-gated calcium channels? |
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Definition
| increased presynaptic calcium permeability |
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Term
| When calcium moves down a strong gradient, does it influx into or efflux out of the cell? |
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Definition
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Term
| Release of transmitter occurs due to ______ of vesicles |
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Definition
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Term
| When transmitter binds to receptor, what two things react? |
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Definition
| transmitter & postsynaptic potentials |
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Term
| How long does it take for the arrival of an action potential to cause vesicle release? |
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Definition
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Term
| Is there a huge or tiny calcium gradient? |
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Definition
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Term
| Katz experiments - part 1 (conclusion: calcium must be resent when the stimulus happens to get the response...calcium is necessary) |
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Definition
1. put a neuromuscular junction in a container & took out nominally all of the calcium from the liquid surrounding the NMJ --> you still get mEPPs, but after a stimulus you get no EPPs
2. puffed calcium onto the NMJ presynaptic cell via a puffer pipette after the stimulus --> same results as before
3. puffed calcium onto NMJ presynaptic cell via a puffer pipette before stimulus --> you get EPPs & mEPPs |
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Term
| Katz experiments - part 2 (conclusion: calcium is sufficient for vesicle release...you don't need an action potential) |
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Definition
1. introduce vesicles (liposome) filled with calcium into the bath, those vesicles fused with presynaptic cell & release calcium into the cell --> EPPs would occur
2. did the same thing with ionophores also
3. caged calcium --> solved the problem of the other two methods being slow
4. no matter which method you use, you get dramatic increase in mEPP/EPP current |
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Term
| conclusion made from Katz parts 1 & 2 experiments |
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Definition
| calcium is the thing for release of the vesicles |
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Term
| 2 ways the cell keeps intracellular calcium levels so low |
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Definition
1. Ca-Mg-ATPase
2. Na-Ca-exchanger |
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Term
| Why if you inject calcium into the presynaptic cell you don't get vesicle release? |
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Definition
| the reason that this is different from the Katz experiments is that they are not a natural situation & there is just so damn much calcium the buffers don't work |
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Term
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Definition
| prevent calcium from acting on the vesicles |
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Term
| 2 natural calcium buffers |
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Definition
1. endoplasmic reticulum
2. mitochondria |
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Term
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Definition
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Term
| How does the cell overcome calcium buffers? |
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Definition
| the calcium channels must be close to where the vesicles are released |
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Term
| conclusion reached from studying the calcium domains on the NMJ at the end of the squid giant axon (acts really fast because it is really big) |
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Definition
| as soon as you stimulate presynaptic neuron, calcium comes in highly concentrated at the "active zone" (active zone is essentially right where presynaptic neuron synapses onto postsynaptic neuron) |
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Term
| You need about _______ micromolar calcium to have this vesicle release happen |
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Definition
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Term
| Where must calcium channels be located? |
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Definition
| on the membrane of the cell quite near the vesicle |
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Term
| Is concentration of calcium in the presynaptic neuron homogenous? |
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Definition
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Term
| short-term synaptic plasticity |
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Definition
| a short-term change in the wiring of a circuit of neurons |
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Term
| Are action potentials in isolation? |
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Definition
| only very rarely (why in experiments they stimulated & recorded a few pulses) |
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Term
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Definition
| opposite of long term potentiation (LTP) |
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Term
| Why do EPSPs get bigger in short-term plasticity? |
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Definition
| if you have vesicles available & calcium built up (ex. paired-pulse facilitation) |
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Term
| Why do EPSPs get smaller in short-term plasticity? |
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Definition
| if there are very few vesicles left (even if you have residual calcium) (ex. paired-pulse depression) |
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Term
| similarity between voltage-gated sodium & potassium channels & voltage-gated calcium channels (VGCCs) |
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Definition
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Term
| fundamental difference from voltage-gated sodium & potassium channels with voltage-gated calcium channels (VGCCs) |
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Definition
| localization of calcium channels is super important; need to be tightly associated with the vesicles |
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Term
| 5 types of voltage-gated calcium channels (VGCCs) |
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Definition
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Term
| How do you identify which types of calcium channels are found in a cell? |
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Definition
| over time, you record EPP size (EPSP size) while you stimulate once about every 1 or 2 seconds & introduce one of the blockers; if the blocker causes EPPs at effectively 0 size, then the channel associated with that blocker is present |
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Term
| Is it possible to have more than one type of calcium channel on a cell? |
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Definition
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Term
| Where do the names for each type of channel come from? |
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Definition
| the first names of the scientists' (who discovered them) children (lol) |
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Term
| difference between L & T channels |
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Definition
L channels open slowly
T channels open right away but only for a short period of time |
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Term
| Does N have a very high or very low threshold? |
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Definition
| very high...needs a high depolarization |
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Term
| Why are P/Q channels linked together in name? |
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Definition
| they are functionally similar enough to be clumped together |
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Term
| What happens to N channel EPSP size over time? |
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Definition
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Term
| Is the number of calcium ions required for vesicle release a linear or nonlinear process? |
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Definition
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Term
| another name for a polarized membrane |
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Definition
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Term
| another name for depolarized membrane |
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Definition
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Term
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Definition
| polarized membrane --> depolarized membrane |
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Term
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Definition
| depolarized membrane --> polarized membrane |
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Term
| inactivated closed --> resting closed |
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Definition
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Term
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Definition
| open --> inactivated closed |
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Term
| Can channels be closed either from extracellular or intracellular? |
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Definition
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Term
| ______ causes channel to open |
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Definition
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Term
| 2 reasons calcium tail currents occur |
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Definition
1. calcium channels are slow to close & high driving force
2. at -65 the driving force is so high that there is residual depolarization (even after voltage step is over) |
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Term
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Definition
| continued current after voltage step has stopped (THINK: IV plots) |
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Term
| Tail current is similar to ______ |
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Definition
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Term
| How do voltage gated calcium channels affect potassium channels? |
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Definition
| calcium enters the cell & activates the potassium channel |
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Term
| effect of a Kv blocker on AP |
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Definition
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Term
| effect of a Kca blocker on AP |
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Definition
| makes reactivation of AP slower |
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Term
| Lambert-Eaton Myasthenic Syndrome |
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Definition
| an autoimmune disease affecting ~1 in 250,000-330,000 people |
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Term
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Definition
| debilitating muscle weakness that temporarily improves with exertion |
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Term
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Definition
| autoantibodies vs P/Q type calcium channels remove them from the terminal |
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Term
| why is there strengthening of muscles with movement in people with LEMS? |
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Definition
| when you keep sending the signal to move a muscle, calcium builds up |
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Term
| How does 3,4-DAP (Firdapse) work to treat LEMS? |
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Definition
| selective blocker of presynaptic voltage-gated potassium channels --> broadening of action potential --> more calcium channel openings --> more calcium influx --> more ACh release --> strengthened muscle contraction |
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Term
| How does GV-58 help LEMS? |
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Definition
| GV-58 prolongs channel opening...leading to increased calcium influx |
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Term
| rationale behind combination approach of GV-58 & 3,4-DAP to treat LEMS |
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Definition
GV-58 works only on open channels; 3,4-DAP increases the number of channel openings
GV-58 takes advantage of additional open channels
3,4-DAP increases GV-58's effect |
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Term
| Are mEPPs affected by LEMS? |
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Definition
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Term
| difference in EPPs between control & LEMS mice |
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Definition
control: nice big EPP
LEMS: very small EPP |
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