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Gillian Mac Kay

PSL302 Audio Lecture NotesLecture 1 Lecture 2 First step in generating a membrane potential voltage is to create a concentration 2gradient in specific ion species ATPases ie NaK Ca generate concentration gradient across cell membraneSecond step is to make membrane semipermeable so that one ion specie can cross the membrane It can diffuse down its concentration gradient building up a charge towards the size I ts moving towards creates an electrical gradientFor the first step NaK pump mainly used3 Na moves outward 2 K move in so its more efficient for Na than KK is more concentrated inside cell and Na outsideExtremely important in maintaining the viability of the cells13 of the metabolic energy consumed goes to the pumpIn nervous system 23 of energy consumed by the neuron is used for pumpThe major purpose of the pump is to create a concentration gradient for Na and Kbc pump is more efficient for Na there are more cations outside than insidethe size of the potential difference between Na and K is 10mV Inside has fewer cations than outsidethe actual resting potential across the cell membrane is larger than 10mV bc the membrane is semipermeable to K bc K is pumped in there is a higher concentration of it inside than outside so K leaks outside down its concentration gradientthe outward diffusion is through channels the specific family is called the twopore channels bc they have two pores built side by side K diffuses out through these pores and accumulates on the outer surface passive diffusion down the concentration gradient The NaK pump pumps it back into the cell The constant diffusion of K outward is responsible for the potential differencethe potential difference is very localized at the membraneNaK pump is responsible for concentration gradientEventually the positive charge outside will be strong enough that there will be electrostatic repulsion preventing any further diffusion of cations outward We have reached an equilibrium stateThe size of the potential that is required to counterbalance the chemical concentration gradient depends on the original size of the gradientYou can calculate the electrical potential difference from the given concentration gradient by the Nernst equationAt equilibrium there is a balancing of chemical work down the concentration gradient and electrical work in the opposite direction at equilib they balance each otherThe concentration gradient that the NaK pump produces is constant for the most partThe equilibrium potential is proportional to KoKi1Faraday is the charge per mole of univalent ionThe potential difference that the diffusion of K will produce is 90mVIn heart muscle cells theresting potential is close to 90mV this tells you that the diffusion of K is responsible and nothing elseIn other cells like neurons the resting potential is around 7065mV meaning something else is involved ie ClTo bring all the ions together in an equation use the Goldman equation takes in permeability of membrane some Na and Cl leak in the major factor is still Kif taking into consideration only Na there will be an accumulation of cations inside the membrane giving a value of 50mVIn order to produce these potentials you only need the flow of a few ions And the pump is constantly working so the concentration gradient is relatively constant zilchSo it requires a constant diffusion to maintain the membrane potentialIf you were to inject a lot of K into the ECM cancelling the concentration gradient the pump has produced the membrane potential would go to zeroIf you were to open Na channels there would be a net movement inward until there is repulsionCl ions are more concentrated in the ECM like Na its no due to active pumping its due to proteins in cell are net negative and repel anions Cl so there is an inward concentration gradient for ClThe Na channel is voltage gated it requires a change in the potential difference a depolarisation The fourth segment of a transmembrane protein is usually charged and moves according to a change in the membrane potentialIf the membrane potential is reduced from 70 to 50 that is sufficient to cause a conformation change in the Na channel so that it opens up a pore allowing only Na to move inThe Na channel has a lot of appendages One is called the inactivation gate bc after about 1ms it comes to a resting position right across the pore blocking Na from entering So the diffusion of Na is very briefThe Na channels occur in high density in excitable membranes When the channels are open there is a large inward current of Na bc there are so many channels so the membrane potential spikes But it never reaches 50mv bc there is constant diffusion of cations and the channels are only briefly openso you have a resting potential then the membrane potential reaches 50mv causing Na channels to open then you get a spike then the channels close bc the potential is so far from the resting potential of K there is a large influx of K causing the potential to go back down This entire event is known as an action potentialthe Na channels are permanently inactivated until they reconfigure to their original shapes which is when the membrane potential goes back to below threshold If you dont repolarise the membrane you cant open the channels again and theyre stuckBc the Na channels become inactivated you cant generate another spike for some time 2The absolute refractory period is when you cannot generate a AP at all This is the time from Na inactivationuntil it reaches threshold potential Bc Na channels repolarise at different speeds you get a relative refractory period where some Na channels are open so you get a stunted spikeIf you prevent repolarisation injecting a lot of K into ECM the Na channels remain inactivated so you cannot produce an AP fatal depolorisation blocka constant absolute refractory periodSome strategic membranes have extra K channels which increases the outward K diffusion allowing for a faster repolarisation and also cause afterhyperpolarisation after bc it occurs after threshold which is only temporarily It hyperpolarises due to the slow kinetics in closing the channels The K channels have the same threshold as Na but bc they have slow kinetics move slow they only open after the Na channels have been inactivated so they dont interfere in the spikeLecture 3 Friday At the sight of an action potential where the Na channels open you get a reverse of polarity where there are fewer cations outside than insideThe positive inside compared to outside will spread along the membrane causing other channels to open the source of depolarising current to the surrounding membrane It opens voltage gated Na channels in adjacent membraneThe spread of current is the same as that in a copper wire a passive spreadIf there are no Na channels then the cell is not excitableExcitable neurons tend to have long axon to carry AP from one place to another Muscle cells tend to aggregate into long fibres which can conduct AP long distanceAxon is the excitable tissue in the neuron where the Na channels are located The dendrites dont have Na channels there are some in the somaThe AP starts at the initial segment of the axon once started they will propagateAt the end of the axon there is an enlargement called boutonThe axon regenerates the signal by opening Na channels as long as the signal passes thresholdThe length constant of the membrane lambda Lambda is a measure of how quickly a potential difference will decay to 0 if lambda is short that means it drops quickly if there is good conductance then the decay is slow so you want lambda as large as possibleTwo strategies to increase lambdaIncrease axon diameter The larger the diameter the easier the current flows through less resistanceIncrease the membrane resistance so that current cant leak across membrane This is the most powerful strategy to increase lambda Done using glial cells which wrap around the outside of the membrane to increase the number of membranes layersSince the external resistance the resistance of the EC fluid is quite low its not needed in length constant equation3
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