Neurophysiology Study Guide - Exam 2
Neurophysiology Study Guide - Exam 2 NSC 4356
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This 6 page Study Guide was uploaded by Christine Thomas on Tuesday March 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 93 views. For similar materials see Neurophysiology in Neuroscience at University of Texas at Dallas.
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Date Created: 03/01/16
Study Guide – Neuro Phys Exam 2 Exclusive potassium dependence of the membrane potential in cultured most oligodendrocytes If you increase the resting membrane from out side the cell What happens when you increase the Multiple questions of this on the exam DEPOLARIZES – resting membrane B – trying to decrease extra cellular sodium increase in choline no dependence on resting potential of sodium D – to change the external concentration to create any kind of change Ouabain – toxin when you poison K atpace – membrane potential will end up being 0 If you wanna force cells to depolarize – by putting a whole lot of something Voltage Clamp Currents in a Squid Axon Have voltage camp it injects current at one way or another trying to measure membrane currents See what kind of current you get – inward or outward Downward deflection – inward current – pos charge into cell Upward deflection – outward current – pos charge out of cell Squid is being clamped at -65mV Hyperpolarize it No kind of current found From -65 to 0 (depolarize) First an inward current and then a slowly developing outward current (inward sodium current for a short period of time to outward postassium current that lasts longer) Hodgkin and Huxley They make all kinds of predictions When you depolarize cell you get transient current coming inward and later going outward – we should be able to separate those out If this initial deflection inward is sodium – then you should be able to take away sodium and replace it with choline then the inward current should disappear Sodium and potassium are doing different things at different times Family of Voltage Clamp Currents Bring to minus 10 then that’s the inward current that later becomes an outward current Plus 10 is the same Pattern is the same until you get to plus 70 The size of the inward current keeps getting smaller Fits with hypothesis that diagram has to be sodium If you take the amp of these and plotted them according voltage- you would generate a current voltage plot Macroscopic channel currents are the sum of currents flowing through many individual channels Microscopic current How much current is going into the channel You can average it all – Density is different depending on where you look Nodes especially have different densities Replacement of Na+ Two hypothesis I think that’s a sodium current Clamp cell at sodium equilibrium channel Replace sodium with something else – same charge but bigger You see classic pattern inward sodium current that later becomes an outward potassium current When you replace sodium with something else then the sodium current basically completely when away H.H. Membrane Model Modified circuit diagram – Hodgkin and Huxly I – is a current (C is compacitance – so its compacitance current) Any time charges are moving is a current L is leak – leak conductance , resistor and battery – leak is some what similar to K Size of leak current will change Leak battery (its K) is the same as the K battery – notice they are the same symbol Conductance is higher when open K is always open – they don’t change Conductance Changes Measuring conductance overtime We know how to isolate currents What is the change in Na current As the number changes the conductance change but they inactivate quickly but after a while the conductance doesn’t change as much as it reaches 23-44mN You have opened all the Na channels so there wont be a big difference in the conducatance – they saturate K conductance The conductance increases as the numbr get bigger but after a certain number they stop getting bigger Voltage Dependence of Ionic Conductance Not much change in conducatance on membrane Membrane Dynamics bring it back or later gNa – if you leave it there at 9 mV what will happen- the conductance will go up If you leave it after where the channels have turned off will not really make a difference If you bring it early – rise in Na conductance but will come back down – if you take that away then it will come back down – this is cause of the change in voltage This is cause you left the cell depolarized All the channels deactivate (later) Current voltage relations of Squid axon Slope on the ib plot is conductance Slope of line is the conductance of the membrane at that point (the red lines) Line should be getting steeper Anything that you do to the right of the last line is basically = no change cause you have maxed out the conductance Moving left to right you are getting bigger conductance Channel structural elements: gates Drawing is the lipid bilayer If you look tat in half you can see a gate that is closed when the membrane is negative – sodium conductance is low and Respond to change which lets it open or close Inside of membrane is neg and inside of cell is pos then they are attracted But if the membrane is pos and the inside of cell is pos then the cell will open cause the inside is trying to et out Inactivation gate – a ball of chain – will move up into the pore and clog the pore even though the activation get is open – channels still open Membrane still pos in the inside except the ball blocking the channel Na channels open really quickly after depolarization Slow part is when the channel becomes neg again – what you normally waiting on in neurons that are trying to fire action potentials quickly which takes forever Structure of a bacterial voltage gated sodium channel pore reveals mechanisms of opening and closing One crystalized in open state and one crystalized in closed state Intracellular side – bottom of channel That hole is where the sodium comes through When channels open there is more space in the gate than that when it is closed Where is the get on the channel – toward the center of the cells Two-pulse Voltage-Clamp Experiment Pre pule in themidle and then a second pulse at the end Start at -70 and then hyperpolarize it to -90 then bring it up to 0 and see what happens Not much is going to happen btwn -70 to -90 Then I when you go up to 0 you would expect that there would be a big current This is a Na current The second biggest one would be the -30 Huge difference btwn the -30 and -90 mV Two-pulse Voltage-Clamp Graphing data from the slide before H is the probability not activated Na current after -15mV to a larger number names the current to become smaller They probably are mostly inactivated Done worry about the thinner line What will be the fraction of what stage that they will be at First line Probably not really inactivated Probably mostly at rest – a ton of yellow Last line Probably inactivated – cause more red Doesn’t mean every channel in that state – obviously they are at different states – its always moving Rate of Recovery Amount of time it takes to recover all the Na channels will be slower cause you have to get back to They would recover faster at -90 than it -75 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 Create a model to predict what the channels were doing X-axis is time 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 Phases of the Action Potential Membrane is leaky to potential at rest We are starting at rest cause conductance at rest is higher during this period of time – rest potential channels are always open – they are not voltage sensitive Increaseing permeability of K – it will do a better job at pulling its potential to equilibrium easier You have extra K channels open – which are the voltage gated channels – giving it more paths to get out of the cell Conductance of membrane with these channels Where is rest in this cell? Threshold Magical moment in time when you hit that point and the voltage gated channels open If threshold is higher up – you have to get up there – so you need some kind of depolarization 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 – its 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 sesium 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 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 appy it to the outsie 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 TXT and STx insensitivity on the sodium channel II Specific amino on specific part of the protein (amino acid) that if you mutate it you loose the +bility to use TTX and STX Pharmacology of Na Channels TTX – most commonly found in puffer fished – from reorganisms 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 ( out side of the channel – sits on the outside of channel as a plug and so Na cant 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 gong 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)
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