Action Lab Simulations

Abstract
This article is investing the effects of speed of the action potential across many neurons through investigating two diseases and performing related lab simulations. Multiple sclerosis and epilepsy are the two disease which are investigated and through the use of Neurons in Action lab simulations, we saw the effects that demyelination and channelopathy can have. As my hypothesis guessed, demyelination is the main cause of multiple sclerosis and channelopathy is the main cause of epilepsy.
Introduction
The nervous system is susceptible to many disease and disorders. Nervous system degenerative diseases are those where neurons, parts of neurons, or any part of the nervous system become damaged and die. The purpose of this study
is to understand the mechanisms of epilepsy and multiple sclerosis. “The term “channelopathy” was coined by Louis Ptácěk to describe dysfunction of a Na+ channel underlying inherited hyperkalemic periodic paralysis. Since then, the concept of channelopathy has been expanded to cover a number of syndromes with dysfunction of ion channels at their foundation, including myopathy, pain, cardiac arrhythmia, and epilepsy.” (Poolos and Johnston, 2012) My hypothesis was that demyelination is the underlying cause of multiple sclerosis, and channelopathy is the underlying cause of epilepsy. Myelin is made of lipids, proteins, and protective layers of nerve fiber. Myelin functions to insulate nerve fibers and thus speed up action potentials between neurons. Demyelination is degeneration of the myelin. (Canbay, 2010). I performed simulations with a group, and we manipulated factors in the axon to see the effect upon the action potential, if propagated at all.
Materials and Methods Over a series of three labs, my group performed several Neurons in Action Lab Simulations in the following order (with no changes to the original instructions): The Membrane Tutorial (Resting Membrane Potential) (Manipulates which ion channels are present as leak channels), Equilibrium Potentials (Eion) (Manipulates the ion’s resting potential with only one type of ion present, sodium or potassium), The Na+ Action Potential (manipulates action potential by using sodium), Refractory Period (manipulated factors affecting the refractory period), Threshold, Voltage Clamping a Patch (differs pulse length and number of pulses), The Passive Axon, The Unmyelinated Axon (manipulates speed and propagation of action potential with differing amounts of insulation), The Myelinated Axon (shows speed and propagaton of properly insulated neurons), Partial Demyelination (manipulates speed and propagation of action potential with differing amounts of insulation). Each tutorial manipulated different independent variables, as listed below.
Results
The results from the simulations which my group ran are recorded below as required by the worksheets:
Resting Membrane Potential
2) Mv at beginning: 0 at end: 200, after current the current pulse, mV remains constant at 200mV
3) Vm is 75 lower at all points than #2.
Starts at -75mV and ends up at 125mV staying constant at 125mV.
4) It is similar I that the charge becomes more positive before reaching a maximum. However, the changes are much less pronounced, and, with the addition of leak channels, the membrane can repolarize after the stimulus current has ended. The graph shows the Mv going from -70 to -7 to -50 (and still decreasing).
5) This graph has three spikes (the second being slightly less drastic, and the third being very slight). One from -65mV to 50mV to -73mV followed by the other from -65mV to 30mV to -73mV. The third spike looks similar to the graph in #4. The voltage-gated channels have an inactivation gate for sodium which closes at specified mV and the membrane repolarizes before initiating another action potential.
Equilibrium Potential
1) Because there are no sodium
channels.
2) EK became more positive. The value of EK is not equal to the membrane potential.It changed in the positive direction because there was an increase in potassium, which has a positive charge. 124mM of extracellular potassium is needed to reach an EK of 0.
4) Intracellular (Mm)= 124: -77.3 500: -110.9 5: 0 Extracellular (Mm)= 124: 0 500: 33.6 5: -77.3 Yes, the equation works because we only working with a one type of ion.
5-8) Repeat 1-4 for sodium
1) Because there are no potassium channels.
2) ENA became more positive. The value of ENA is not equal to the membrane potential. It changed in the positive direction because there was an increase in sodium, which has a positive charge. 124 mM of extracellular potassium is needed to reach an ENA of 0.
4) Intracellular (Mm)= 24: 42.5 14: 55.4 4: 8.6 Extracellular (Mm)= 180: 61.5 140: 55.4 100: 47.3 Yes, the equation works because we only working with a one type of ion.
9) -10.9 mV/ -65.2, close to EK/ 43.4 closer to ENA
10) 52.2MV
EK 124: Vm= -74.0 EK= -77.3/ 500: Vm= -106.8 EK= -110.9/ 5: Vm= 1.4 EK= 0
ENA 500: Vm= -73.3 ENA= 86.1/ 124: Vm= -74.1 ENA= 52.5/ 5: Vm= -76.0 ENA= -24.8
1)
A.
The Vm rapidly depolarizes, then slowly curves upward (depolarizes) before the graph line becomes almost vertical followed by steadily repolarizing and, lastly, hyperpolarizing. Because this is the way an action potential works.
B. The currents are almost identical reflections except for, at the beginning of sodium influx, there is a drastic influx spike from about 0.7ms to 1.3ms and -44mV to 45mV.
C. Sodium conductance has a sharp spike (almost vertical line to a steady decline, reaching a top of approximately 0.034), however potassium (which peaks at 0.013) is a gentle rise and decline. Sodium conductance peaks at the same time as the membrane voltage. The potassium conductance begins to increase at about 0mV. The sodium conductance begins to increase at -34mV. Sodium movement is much higher at the beginning. Potassium is gradual from middle to end.
D. 3.8ms to 5ms (end of graph). Sodium current is reaching zero, then stays at zero as driving force reaches and maintains zero current as well.
2)
A. No question in this
part
B.The duration is significantly shorter, about 1/3 the time for each. The conductance and thus current for sodium did not become as high for the room temperature setting, but potassium got slightly higher
3A) Sodium Channel Density: 0.001875 S/cm^2
Potassium Channel Density: 0.0005625 S/cm^2
4A) It is greater than lidocaine at 0.0075.
5A) The TTX remains latent for longer, but reaches a higher peak magnitude than lidocaine. Both TTX and lidocaine greatly reduce the amplitude of the action potential (AP) and current of both ions. TTX terminates the AP sooner than lidocaine and this could account for its stronger paralysis effect.
6A) There is a quick, slight increase in Vm from the second pulse, but it does not generate an AP lik the first pulse. IF I increase the delay of the second pulse to 11 seconds (the refractory period) then a second AP can be generated by the second pulse.
7)
A. 55Vm
B. Yes, the threshold is the same. Yes the AP initiated soone. The Vm threshold for an AP is mV at which the AP is generated (the point at which the mV begins to exponentially increase).
8)
A. At 6.0 °C an AP is initiated, and at each 0.1°C lower increment the AP was generated more quickly.
B. Threshold at 20°C is 11nA and -64mV. The Vm at which the AP is generated at current aplitude and temperature.
9)
A. Include the duration of the pulse as a factor.
B. (0.1ms) 85mV vs. 43mV (0.2 ms)
C. 1ms: 9nA 5ms: 3nA 10ms: 2.5nA 15ms: 2.5nA
10A) Sodium peak is -16mA/cm^2. The duration of the graphs is the same. The slop of sodium is greater. It shows that the sodium influxes before the potassium efluxes.
11)
A. Because resistance has to change, since voltage is held constant and current is increasing. V=IR
B. 1) Because conductance is rising 2) If current is 0, then the conductance becomes 0.3. To restore resting membrane potential.
12) Larger, that potassium is more important for regulating resting membrane potential

Discussion
Myelin is a fatty, insulating substance which can be found on the axons of many neurons. Multiple Sclerosis (MS) is an inflammatory disease in which parts of the nervous system become inflamed and/or damaged resulting in wide range of symptoms. A major underlying cause of MA is demyelination or the removal/destruction of myelin sheaths and, thus, slowed communication and eventual injury to the affected axon. Oligodendrocytes are often also attacked, perhaps as part of immune response. However, the pathogenesis of all these effects is unknown (Bitsch, 2000 p. 1174) Eventually many axons have been demyelinated and adverse effects become obvious if the affected individual, but MS can have nearly any symptom which would be controlled by the nervous system, the symptoms correlating with the most damaged areas. Furthermore, axons contain sustain injury after the degeneration of the protective myelin sheath and this can be a key factor in the effects of demyelination (Bitsch, Schuchardt, Bunkowski, Kuhlmann, Brück, 2000). Channelopathy may also be a cause for cerebellar dysfunction in multiple sclerosis. (Minagar, 2012) Evidence for HCN channelopathy in human epilepsy is thus far limited. Since virtually all clear-cut evidence for any ion channelopathy in epilepsy derives from the inherited or genetic epilepsies (Poolos, 2010). However, evidence still suggest that other type of channelopathy are present in some acquired epilepsies.
References
Bitsch, A.. "Acute axonal injury in multiple sclerosis: Correlation with demyelination and inflammation." Brain 123.6 (2000): 1174-1183. Print.
Canbay, Cahit. "The Essential Environmental Cause Of Multiple Sclerosis Disease." Progress In Electromagnetics Research 101 (2010): 375-391. Print.
Minagar, A.. "A Channelopathy Contributes to Cerebellar Dysfunction in a Model of Multiple Sclerosis." Yearbook of Neurology and Neurosurgery 2012 (2012): 69-70. Print.
Poolos, Nicholas P.. "HCN channelopathy in epilepsy." Epilepsia 51 (2010): 12-12. Print.
Poolos, Nicholas P., and Daniel Johnston. "Dendritic ion channelopathy in acquired epilepsy." Epilepsia 53 (2012): 32-40. Print.