Nimble Nerve Impulses OO-005-DOWN

Nimble Nerve Impulses OO-005-DOWN We d love to hear any feedback, comments or questions you have! Please email us: info@ Find us on Facebook: facebook.com/origamiorganelles

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Introduction Nimble Nerve Impulses Nerve impulses are the messages nerve cells send to one another. These impulses are the basis of all nervous communication and the essence of our very thoughts. Nerve impulses are created by very fast movements of ions through highly specific ion channels embedded in the neuronal plasma membrane. To understand these impulses, we must look at nerve cells in both their resting state (resting potential) and active state (action potential). Resting potential There are two aspects to the resting potential, a chemical gradient and an electrical gradient. Chemical gradient due to the sodium-potassium pump Sodium ions (Na + ) and potassium ions (K + ) are unequally distributed between the inside and outside of a neurone membrane causing the inside to be negative. It is a small difference that is measured in millivolts (mv) but it is enough to drive the communication in all nervous systems. The K + concentration is higher inside the cell (140mM) than outside (5mM), whereas the Na + concentration is higher outside (150mM) than inside (15mM) the cell. This concentration (or chemical) gradient is a source of potential energy so it is called the membrane potential. In a resting neurone the membrane potential is about -70mV. This chemical gradient is maintained by the sodium-potassium pump. The sodium-potassium pump is an ATP driven pump that actively transports Na + out and K + into the cell against the electrochemical gradient. Three Na + are pumped out for every two K + it imports. This movement drives a net electric charge across the membrane so the inside is slightly more negative than outside. As the membrane potential is only due to movement of a small number of ions near the membrane, it has no effect on ion concentration in the cell overall. Electrical gradient due to the potassium leak channels As the name suggests, leak channels allow a free flow of specific ion through the plasma membrane. Potassium leak channels use the concentration gradient to establish the resting potential. The K + concentration is much higher inside than outside so there is a net outflow of K + along the concentration gradient. Na + leak channels are also present but fewer are open than K + leak channels. Thus, this movement of K + outward and inability of Na + to enter causes a net movement of positive charge outside making the inside negative relative to the outside. This stops when the attraction of the negative charge inside the cell opposes the outflow of the positive K + ions, so the electrical gradient counterbalances the chemical gradient of K +. 3

The equilibrium point between the chemical gradient on one hand and electrical gradient on the other, can be calculated using the Nernst equation. For K + at physiological concentrations, it has an equilibrium potential of -90mV. For Na +, it is +62mV. The resting potential of neurones at -70mV is close to the K + equilibrium potential but not as low because there are some Na + leak channels to make it less negative. Once the three dimensional structure of the K + leak channel was worked out by X-ray crystallography, it showed how leak channels can distinguish between the very similar ions Na + and K +. The K + ions interact with four groups inside a narrow part of the channel that are too far apart to interact with the Na + ions. We will now turn to the neurone when it conducts a nerve impulse. Action potential An action potential is a travelling wave of depolarisation that quickly moves along the neurones plasma membrane in one direction. It is very fast at over 260 miles per hour! Gated ion channels open or close to cause a change in the membrane potential. This creates a pulse like signal (the nerve impulse) that conveys information around the nervous system. Depolarisation is a reduction in membrane potential that can be caused by a synapse activating or a generator potential caused by a sensory stimulus. For a depolarization to cause an action potential, it must bring the inside to, or beyond, the threshold potential of -55mV. If this happens, voltage gated Na + channels open and Na + diffuses into the cell along its concentration gradient. This self-amplification increases the depolarization further, so it is a type of positive feedback. This brings the membrane potential to +40mV. After being open for a short time, the voltage gated Na + channels become inactivated due to a change in their conformation. The channel is blocked by an inactivation gate that is part of the protein. The sodium channels remain in this inactivated state until the membrane is repolarised. This feature of the sodium channels is the reason for the refractory period that separates the action potentials into discrete pulses and also stops them going in both directions. At about 40mV, K + channels open and allow K + to rapidly diffuse out of the cell. This cancels out the Na + influx and makes the interior of the cell more negative relative to the outside. Thus, the cell becomes repolarised. When the voltage is just below the resting potential (at about -80mV), the K + channels close. The channels have voltage sensors that are made from four alpha helices with numerous positively charged arginines. This is known because scientists have worked out the three dimensional structure of the protein using X-ray crystallography. Using ATP, the sodium-potassium pump now corrects the balance of Na + and K + ions across the membrane and restores the resting potential to about -70mV. 4

Conductance of an action potential This happens in a small patch of plasma membrane. This self-amplifying depolarisation is enough to depolarise neighbouring regions of the membrane, which then produce their own action potentials. These rapidly move along the whole length of the axon. Action potentials are unidirectional Action potentials only travel in one direction because the voltage gated Na + channels become inactivated a short time after they have opened and stay like this until the membrane is repolarised. As the Na + channels are shut where the action potential has just been, they block it from going backwards and ensures nerve impulses travel in one direction. Refractory period As has already been said, voltage gated Na + channels are inactivated from the peak of the depolarization until the membrane is repolarised. Thus, if a new stimulus arrives, a further action potential cannot be produced immediately as these channels are unable to respond. This ensures nerve impulses are discrete signals. All-or-nothing principle A depolarisation must exceed the threshold value to trigger an action potential. If the stimulus is not enough, no action potential is created even if it is just below the threshold value. If is strong enough, one is fired even if it is just above or far exceeds the threshold value. Only one action potential is generated however strong the depolarization is as long as it exceeds the threshold. The frequency of impulses indicates the strength of the stimulus. Loud sounds make more action potentials than quieter sounds. By having neurons with different threshold values, it is possible to give a graded response to a stimulus. Wider axons vs myelination Speed of axon conductance is critical to survival so there is a (natural) selection pressure to maximize this. Two solutions have evolved. For invertebrates, wider axons have developed that are faster as there is less resistance. The squid giant axon at an enormous 1 mm wide is the most extreme version of this! For vertebrates a different solution has emerged. The axons of vertebrate neurons are insulated by a myelin sheath that greatly increases the speed and distance of conductance of the depolarisation. Myelin is formed by glial cells. Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. These cells wrap many layers of their plasma membrane around the axon in a spiral. This electrical insulation enables the depolarization to spread much further. The axons can also be thinner as much less space is needed than in the squid giant axon. 5

To increase speed even further, the impulse can jump between gaps in the myelin called nodes of Ranvier. These occur every 1mm and are where most voltage gated Na+ channels are to be found. This jumping of the depolarisation from node to node is called saltatory conduction. This speeds up transmission and less energy needed as only small regions of plasma membrane need to be excited. The medical condition multiple sclerosis (MS) demonstrates the importance of myelination. MS happens when myelin is lost in some parts of the central nervous system causing slower nervous conduction leading to severe neurological difficulties. Temperature affects the speed of conductance Temperature affects the diffusion rate so there is faster conductance when an axon is warmer. Energy for active transport is produced by enzyme driven respiration. This will be faster in a warmer environment as long as the enzymes are not denatured. Cold blooded (ectothermic) animals are affected by this in cold environments. Using depolarization to study neurone function Genetic engineering techniques are becoming increasingly useful when studying neuronal function. The field of optogenetics uses light activated ion channels called channelrhodopsins to depolarise cells with extreme spatial and temporal precision. When channelrhodopsins have been genetically engineered into the hypothalamus of mice, violent behaviour can be induced by using light to specifically depolarise neurones thought to be involved in aggression. 6

Nimble Nerve Impulses - Lesson Guide Components Cell membrane Sodium ions blue Potassium ions yellow Myelin sheath Voltage gated Na + channel gate Velcro 1cm hook and loop (not included) Make model Follow instructions on Assembly Guide. Resting potential activity Show resting potential with model. Balance between chemical gradient and electrical gradient. For our model, we will assume each ion represents a movement of ions that shifts the membrane potential by 10mV. 1 Chemical concentration gradient The sodium-potassium pump establishes this as it pumps out three Na + for every two K + it imports. It does this using ATP as it is working against the concentration gradient. Put the ions in following ratios on inside and outside of resting potential membrane model: K + Na + Out 0 11 In 19 0 2 Electrical gradient K + leak channels use the chemical gradient to create an electrical gradient. We show this by moving seven K + from the inside of the membrane: K + Na + Out 7 11 In 12 0 This movement of ions establishes -70mV inside the membrane relative to outside. That is why you can get this charge difference even though no negative ions. Not enough movement if ions to alter concentration gradient of ions overall as only a very small number of ions are involved. Both K + and Na + voltage gated channels are closed. You can model this by using the Velcro to close the channels. Ungated channels maintain resting potential. The membrane potential will change rapidly if the membranes permeability to an ion changes. It will tend to move towards the equilibrium vale for that ion. This is what happens in an action potential. 7

Action potential activity An action potential means nerve is conducting an impulse. We begin with the same ion distribution as for the resting potential with the membrane potential at -70mV. 1 Depolarisation due to stimulus at synapse or generator potential from a sensory cell opens some Na + channels causing an influx of Na + ions that depolarise the membrane. Show this by moving two Na + ions from inside to outside: K + Na + Out 7 9 In 12 2 In our model, one ion is not enough to cross the threshold (-55mV) so you need to move in two. This brings the membrane potential to -50mV. If only a small stimulus happens, the threshold may not be passed and no action potential would arise. If it passes the threshold, an action potential would be triggered. It does not matter by how much the threshold is exceeded, you just get one action potential. 2 Rising phase begins. If the threshold is passed, voltage-gated Na + channels open. Na + ions enter the cell along their concentration gradient. This is an example of positive feedback. Show the depolarisation by moving nine Na + ions from inside to outside: K + Na + Out 7 0 In 12 11 This changes the membrane potential to +40mV. The voltage gated K + channels remain closed during the rising phase. 3 Falling phase starts. This starts when voltage gated Na + channels become inactivated by a protein gate that blocks channel. Show this on the model by blocking the sodium channel with the arm. Note the Na + voltage gated channel is still open, but is blocked by the protein gate. Thus, these channels have three states, open, closed and inactivated. At +40mV, voltage gated K + channels open and the K + ions move along their chemical gradient out of the cell making the inside negative. Show this by moving 12 K + outside: K + Na + Out 19 0 In 0 11 4 Hyperpolarisation. K + outflow makes the inside -80mV. Voltage gated K + and Na + channels close show this with the Velcro. 5 Repolarisation. Sodium potassium pump restores resting potential of -70mV. It moves three Na + out and two K + in using ATP. This all happens very quickly in just a few milliseconds so a nerve call can fire hundreds of impulses per second. 8

Myelin sheath You can model this by wrapping the axon with the myelin sheet provided. The action potential would jump to the next Node of Ranvier because the depolarisation has spread this far to initiate a new action potential. Optional activities 1 Students can join their axons together to show how the salutatory conductance works. 2 Join the nerve impulse model to the synapse model to show how depolarization is triggered. 3 Use the synapse set to create a neural network by making neurones that form synapses with each other. 9

Colour Assembly Guide Makeions,myelinandchannelgate 1. Followtheinstruc1onsonthesheets. Makeneuronemembrane 1. CutalongsolidlinesexceptredHshapedlinesincentre. 2. Foldinhalflengthwisealongthedashedlineinmiddle. 3. CutcentreredHshapedlineswithscissorscrea1ngtwoflaps. Cutup 4. Turnsheetover.Tapechannelsidestogether,joiningAwith A,BwithB,andsoon. 5. CuttosizeandaddVelcrohooksorloopstothechannelsas indicatedonthesheet. 6. Foldbackalongdashedlinesformingrectangularbox&tape togetherasshown: 7. ANachtheNa + channelgate(onseparatesheet)bythestem asindicatedonthena + channel. Thefinishedmodel! Then across MAKEANNERVEIMPULSEWITHYOURMODEL Placemodelwithbasedownandinsideofcelltowardsyou Wewillassumeeachionrepresents10mVofcharge GatedchannelshaveVelcrosotheycanbeclosed startwiththemshut ResOngpotenOal Res1ngpoten1alduetobalancebetweenchemicalandelectricalgradients. ChemicalconcentraOongradientQduetosodiumpotassiumpump 1. Distributeionsasfollows:19K + inside/11na + outside ElectricalgradientQduetopotassiumleakchannels 1. Move7K + frominsidetooutside 2. ThisestablishesZ70mVinsiderela1vetooutside=membranepoten1al AcOonpotenOal 1. Depolarisa1onduetos1mulusatsynapseorgeneratorpoten1alfromsensorycell move 2Na + inside.ifthiscrossesthreshold(z55mv)ac1onpoten1alistriggered. 2. Risingphasebegins.VoltagegatedNa + channelsopenduetodepolarisa1on(posi1ve feedback) separatevelcro.move9na + inside.makesinside+40mv. 3. Fallingphasestarts.VoltagegatedNa + channelsbecomeinac1vatedbyproteingatethat blockschannel.youcanshowthiswiththegateonthemodel.voltagegatedk + channels open separatevelcro.move12k + outside. 4. Hyperpolarisa1on.K + ou`lowmakesinsidez80mv.voltagegatedna + channelsandvoltage gatedk + channelsclose showbyclosingwithvelcro. 5. Repolarisa1on.Sodiumpotassiumpumprestoresres1ngpoten1al 70mV. MyelinaOon 1. Wrapmyelinaroundendofmodel. 2. Depolarisa1onjumpsbetweenunmyelinatedareas(nodesofRanvier)sofaster conductancepossible. QUESTIONS 1. Whatestablishesthechemicalconcentra1ongradient? 2. Whathappensifs1muluslessthanthreshold? 3. Whatdrivessodiumpotassiumpump? 4. Howdoinvertebratesmakeaxonalconductancefaster? Origami Organelles! print! make! learn Design 403598

A C E HOOK G HOOK Na + K + pump 3Na +!" 2K + # K + leak channel Voltage gated Na + channel Voltage gatedk + channel A B C D E F G H Baseofmodel Tape gate here Insideofcell Outsideofcell!"!" B Origami Organelles! print! make! learn D LOOP LOOP F exploitation or modification by the purchaser or any third party of H

Ions:cutalongsolidlines,rollupandtapetomakecylinders K + Na + Na + K + Na + Na + K + Na + Na + K + Na + Na + Gatefor voltage gated Na + channel K + Na + Na + K + K + Na + K + K + K + K + K + K + K + K + K + K + K + K + Gate:cutalongsolidlines,rollupwidepart andtapetomakecylinderonstem Myelin:cutalongsolidlines,rollintocylinderthatwrapsaroundneuronemembrane.Tape. Myelinsheath Origami Organelles! print! make! learn exploitation or modification by the purchaser or any third party of

Mono Assembly Guide Makeions,myelinandchannelgate 1. Followtheinstruc1onsonthesheets. Makeneuronemembrane 1. CutalongsolidlinesexceptHshapedlinesincentre. 2. Foldinhalflengthwisealongthedashedlineinmiddle. 3. CutcentreHshapedlineswithscissorscrea1ngtwoflaps. Cutup 4. Turnsheetover.Tapechannelsidestogether,joiningAwith A,BwithB,andsoon. 5. CuttosizeandaddVelcrohooksorloopstothechannelsas indicatedonthesheet. 6. Foldbackalongdashedlinesformingrectangularbox&tape togetherasshown: 7. ANachtheNa + channelgate(onseparatesheet)bythestem asindicatedonthena + channel. Thefinishedmodel! Then across MAKEANNERVEIMPULSEWITHYOURMODEL Placemodelwithbasedownandinsideofcelltowardsyou Wewillassumeeachionrepresents10mVofcharge GatedchannelshaveVelcrosotheycanbeclosed startwiththemshut ResOngpotenOal Res1ngpoten1alduetobalancebetweenchemicalandelectricalgradients. ChemicalconcentraOongradientQduetosodiumpotassiumpump 1. Distributeionsasfollows:19K + inside/11na + outside ElectricalgradientQduetopotassiumleakchannels 1. Move7K + frominsidetooutside 2. ThisestablishesZ70mVinsiderela1vetooutside=membranepoten1al AcOonpotenOal 1. Depolarisa1onduetos1mulusatsynapseorgeneratorpoten1alfromsensorycell move 2Na + inside.ifthiscrossesthreshold(z55mv)ac1onpoten1alistriggered. 2. Risingphasebegins.VoltagegatedNa + channelsopenduetodepolarisa1on(posi1ve feedback) separatevelcro.move9na + inside.makesinside+40mv. 3. Fallingphasestarts.VoltagegatedNa + channelsbecomeinac1vatedbyproteingatethat blockschannel.youcanshowthiswiththegateonthemodel.voltagegatedk + channels open separatevelcro.move12k + outside. 4. Hyperpolarisa1on.K + ou`lowmakesinsidez80mv.voltagegatedna + channelsandvoltage gatedk + channelsclose showbyclosingwithvelcro. 5. Repolarisa1on.Sodiumpotassiumpumprestoresres1ngpoten1al 70mV. MyelinaOon 1. Wrapmyelinaroundendofmodel. 2. Depolarisa1onjumpsbetweenunmyelinatedareas(nodesofRanvier)sofaster conductancepossible. QUESTIONS 1. Whatestablishesthechemicalconcentra1ongradient? 2. Whathappensifs1muluslessthanthreshold? 3. Whatdrivessodiumpotassiumpump? 4. Howdoinvertebratesmakeaxonalconductancefaster? Origami Organelles! print! make! learn Design 403598

Print on pink A C E HOOK G HOOK Na + K + pump 3Na +!" 2K + # K + leak channel Voltage gated Na + channel Voltage gatedk + channel A B C D E F G H Baseofmodel Tape gate here Insideofcell Outsideofcell!"!" B Origami Organelles! print! make! learn D LOOP LOOP F exploitation or modification by the purchaser or any third party of H

Print on blue Gate:cutalongsolidlines,rollupwidepart andtapetomakecylinderonstem Na + Na + Na + Na + Na + Na + Na + Na + Na + Na + Na + Gatefor voltage gated Na + channel Ions:cutalongsolidlines,rollupandtapetomakecylinders Origami Organelles! print! make! learn exploitation or modification by the purchaser or any third party of

K + Print on yellow Ions:cutalongsolidlines,rollupandtapetomakecylinders K + K + K + K + K + K + K + K + K + K + K + K + K + K + K + K + K + K + Myelin:cutalongsolidlines,rollintocylinderthatwrapsaroundneuronemembrane.Tape. Myelinsheath Origami Organelles! print! make! learn exploitation or modification by the purchaser or any third party of