Neuro Phys Exam 3 Study Guide
Neuro Phys Exam 3 Study Guide NSC 4356
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This 8 page Study Guide was uploaded by Christine Thomas on Friday April 1, 2016. The Study Guide belongs to NSC 4356 at University of Texas at Dallas taught by Dr. Dussor in Fall 2015. Since its upload, it has received 52 views. For similar materials see Neurophysiology in Neuroscience at University of Texas at Dallas.
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Date Created: 04/01/16
Neuro Phys – Exam 3 Study Guide HILLE CHAPTER 3 H.H. Model- K+ dynamics Create a model to predict what the channels were doing X-axis is time When we repolarize the cell it will take you to zero conductance 4 particles are being open Four separate subunits of a tetramer to make an ion channel We ended up with n^4 Need these four things for membrane to reach its highest potential M^3 – math didn’t predict what the three things are… it didn’t work out Local Circuit Current When charges flow into cell – they have a couple of choices – the charges coming in and any given charge is either going to go forward or back wards if you go forward – then the choice is whether if it flows down or out of the axon – more likely to go forward toward the length of the axons If it goes back then it the same Not easy for ions to flow out of the membrane You are encouraging charge when you flow down the length – it’s easier – cause there are not that many ion channels open in the forward direction (the ones that are open are the ones open all the time) behind you: have voltage gated ion channels open (more ion channels are open in this direction therefore it is most likely to leak out of the membrane) Separation of Na and K currents by pharmacology Potassium is replaced with cesium Same with poliem with sodium Tetrodoxin classic blocker of voltage gated sodium channels Bath axon with TEA – potassium channel blocker Lost outward potassium current Dose Dependent Relative of saxitoxin Sodium current is in percent How much saxitoxin bathed axons = show how much sodium channels are being open Sides of sodium Only works when you apply it to the outside of membrane not the inside Some kind of protein is letting sodium to come into the membrane and letting potassium out There something unique about this protein A single point mutation confers tetrodotoxin and saxitoxin insensitivity on the sodium channel II Specific amino on specific part of the protein (amino acid) that if you mutate it you lose the ability to use TTX and STX Pharmacology of Na Channels TTX – most commonly found in puffer fished – from reorganizes that it eats – doesn’t harm puffer fish (found in the liver) STX – produces red tide – marine organism (shell fish eat this) – if you eat the shell fish then you could be eating STX Block sodium channels from the outside Blocks the ion conducting pore ( outside of the channel – sits on the outside of channel as a plug and so Na can’t get into the cell) Nine different Na channels V and B – there are frogs that have all kinds of toxins in their skin – if you coat darts with the extract of the skin and shoot something with it – then you are going to manipulate sodium channels and basically kill it A comes from blants ST and SAT – inactivation gate doesn’t work anymore – doesn’t close when it should or open when it should They don’t allow inactivation Modulate Na channels LA – anything that ends with ‘caine” – block ion channels from the inside Work better on channels that open frequently So it needs to be able to get into the cell (so it needs to be lipid permeable in order to block it from the inside) On the inside the gates have to be open for it to actually to work properly If channel isn’t open they don’t work very well as they would if the channel was open (channels are big proteins that are moving) They are used for pain so you back block the feeling of pain – lots of activity in sodium channels when you are in pain – when they channels start opening with pain then they will jump right in and block in the pain A have some kind of Na block Might have 10 mechanisms If you have neurons If you want to decrease neurons – block sodium channels Mess with activation also – no control of opening of Na channels Messes with normal shape and control of VGC Specific Binding What concentration of STX will it take to block all the sodium channels – if one molecule will block a sodium channel (1 to 1) Alpha Subunits of Voltage Gated Channels Need 4 alpha sub units for K subunits to form Know who would not be blocked by TTX HILLE CHAPTER 4 Calcium Spikes They took away sodium and action potentials were pretty much normal Found that they don’t use Na for action potentials but Ca (they are Ca dependent action potentials) TEA and TBA block K to have a more prominate Ca excitability Strontium A.P. in Crayfish Muscle K activated by a rise in an increase in Ca Calcium Channel Properties Not as fast as Na channels Deactivation – (5) lots of divalent ions pass through (7) Change membrane potential – for action potential firing Once Na gets in the cell It just basically carries a charge ++ Ca Channel Subunits 4 domains Each domain has 6 transmembrane segments Charges on the s4 – some kind of change in the protein in order to open the voltage gated channel Beta subunits Gamma and alpha 2 delta subunit – unique Ca channel (not in Na channels) – does not make a pore – you won’t have a hole in the membrane Recruits alpha subunit in Drugs – Gabapentin (anti analeptic) and pregalalbin (used for various 2+ type of pain) Ca Currents There are sub categories As you move left to right – reaching the Ca equilibrium potential Whate2+r extra and intracellular are – they are only in the +60 Influx of Ca controls neurotransmitter release The concentration of Ca on inside is related to the outside by the 4 power If you increase Ca influx (expressing more Ca in membrane or a little bit more Ca influx) Don’t have to take away too much Ca into the cell – there will be a huge decrease in the amount of transmitter release Timing of synaptic events You got to wait for Ca channels to open Longer AP or more AP’s cause greater Ca 2+influx Recording Action potentials and Ca concentration – simultaneously Dye Fura 2 – fluoresce properties – different waves of light Emission properties depends on if it is bound to Ca By knowing the fluoresce dye there is you can tell how much Ca is inside the cell More action potential = more Ca in cell Concept of slide 18 graph relationship of Ca concentration inside of cell and transmitter release Calcium Current and Concentration as a Function of Membrane Voltage Peak actually shifted to the right – Ca channel properties – not as voltage sensitive B – membrane potential that you bring cell to – what the change in Ca will be is the more interesting number More Ca outside = more Ca inside (how much Ca is outside of cell dependent on what is inside the cell) Sensitive to Ca concentration in the big Ca currents As you mot to right you are reaching equilibrium – as you approach this then the current gets smaller If you depolarize the cell so the rise of intracellular is not going to be dependent on extracellular cause you are getting closer to the equilibrium Doesn’t matter how much Ca you have inside (only matters closer to the start of the membrane potential Calcium Current and Concentration as a Function of Membrane Voltage Rather than measure how much Ca rise inside of cell – you instead can find how big is the membrane going to be in the postsynaptic cell Not much Ca influx cause you were to close to its equilibrium potential Where you want it to influx is where there is a lot of Ca coming in Some K and Cl currents dependent upon internal Ca 2+ Difference in how K current looks depending on how much Ca is coming – K current is sensitive to Ca current QUESTION: Why does the control Plot Without Ca influx no Ca doing their thing Ca channels should be open and not to close to equilibrium potential Voltage Gated Ca++ Channel Classifications Not necessary the mag of the depolarization its self High voltage gated Ca channels activated in the more pos mV Slower but sustain current Opened both LVA and HVA (more delayed part) channels Not same sensitive in the plot – some turning on earlier , size of currents are different One big and they open earlier and the other is bigger (more sensitive to voltage) than they open later (less sensitive to volt) Voltage Gated Ca Channel Classifications Three differences Different abbreviation for Ca channels HVA: L (larger currents and lasted longer), N (only observed in certain kinds of neurons), R (resistant Ca channels) currents LVA: T currents (currents that are local and activate quickly and don’t stay on very long) P/Q: cloned R – found splice variants of that channels – splicing the main (R) Voltage-gated Ca ++channels Ca have 3 different number before The Cav1 have 4 and are L type Cav2 have 3 have three different types Cav3 have 3 and are the T type HVA – anything with a 1 or 2 that is higher than -30mV LVA – are Cav3’s and are common resting voltage potential -70mV Don’t have do much to a cell cause they will open relativity early ++ Ca Channel Pharmacology End of drugs end in – pine (which is normally a Cav1 blocker Familiar to words in bold but also know the ending Cav2: p/Q – agatoxin (mega) come from spiders – block selectively 2.1 Lost Ca current…. So extrapalate from that you have Cav 2.1 N – blocked by omega conotoxin (letter and number and come from cone snails) Can synthesize the toxin and is approved in use in humans (synthetized) Used for extreme cases of chronic pain – it’s a peptide (chewable) R - toxin from spiders – have no drugs in humans that blocks Cav3 Weren’t Cav3 Blocked by Ni Used to block seizures From scorpions Be familiar with the numbers and things in bold – for exam Receptor binding depends on state of ion channel Nitredipine binds better to the inactivated L-type Ca channel than when in the resting state. Opening and closing but no going into the inactivated state – which they prefer Concept is state compound dependent Graph shows if you have a pop of cells that are sitting at a holding potential at -80mV (not really inactivating) you can block with nitrendipine Percent of Ca goes down as you increase Nitrendipine Other graph is if you hold cell at -15mV Have more Ca in inactivated state That’s the state this drug prefers so blocks better – enhance ability of drug Gating involves major conformation change in the channel when it opens VS when it is closed Some compounds need access in certain times but can’t cause of the state These drugs are commonly used – taken to lower blood pressure Cause you have Cav1 on smooth muscles – if you can’t get Ca on muscle they cannot constrict and pressure inside muscle goes down If you have HBP you would be prescribed –ipine drugs (don’t really cause problems and are considered safe) Resting membrane very pos – Ca on smooth muscle cells spend most of their time in inactivated state (where as other places the Ca channels aren’t in inactivated state) – it doesn’t kill you cause you take them at a concentration that won’t block Cav1 channels in brain HVA Ca 2+ channel inactivation Compound called EGTA – Ca sequestering compound Not freely floating inside cell No change in the beginning of trace but get less inactivation Ca bound to Calmodulin Can bind directly to Ca channel – promotes Ca channel Self-regulating thing Second graph repeating what we saw above Rather than Ca it is replaced with Ba Ba comes into cell and does not bind to calmodulin cause no Ca influx Ba goes through Ca channel better but doesn’t contribute to Ca channels better HILLE CHAPTER 5 Some of The Roles of Potassium Channels Know what do potassium channels do? K channels subunits Need 4 subunits Take 4 and put them together and now you’ve got a K channel Beta subunits Affect channel prompters Where does the beta subunit interact? To the N terminus β subunits alter current kinetics No inward current here – so family of K currents One – they are expressing the alpha subunit for kv1.5 in a cell line that doesn’t have any other ion channels All kinds of cell lines to express ion channels – now you can study they ion channel (cell) without worrying about isolating it All you have is the alpha subunit Second unit – they also expressed a beta subunit (1.1) When you add the one before with 1.1 – you find that it eventually inactivates unlike the graph above it All you added what the beta 1.1 It know inactivates faster Third and fourth – there is not a big change as there was as in when adding 1.1 When beta 2 and 3 may help get into the membrane Meaning they probably don’t interact with 1.5 (influencing) Structural Similarities Dude showed world what the K channel looks like 4 coming together Choice is made who gets through Neg charges there cause it has to be similar to the waters charges – to make the channel happy Neg charges probably coming from the carbonyl oxygens from the sides of the amino acids K channel structure They are sort of at an angle and point toward the cavity – it is hydrated and then dehydrated and then hydrated again As coming out the pore it is stabilized by one side at first and is starting to get rehydrated Ion channel proteins are not only within the membrane The protein of an ion channel Transmembrane T1 domain - not a ligand channel Has a lot of protein hanging off of it Beata subunit Structural basis of gating Get a better idea of how gating channel actually happen Minimally part of what you need to create a pore Need pore domain Pushing s4 away from cell (out of cell) at +40mV Going to pull on s5 – which is going to change how it is embedding into the membrane which can also change s6 This all happens cause s4 moved (cause the cell became positive) Delayed Rectifier Channels A channel who’s conductance changes after some delay They are slow They are slowly rectifying anything Within the delayed there are fast and slow The fast open relativity quickly (they are shut but inactivation) In this case you use ether
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