Please help me answer these questions 3-11, Thank you!!
NeuroSim Goldman model - Default Eile Model Edit View Window Help Setup Mem Pot -55.97 -100 mV/ Temp (C) Temp 20 BE AZ ? №? +100 mV Relative permeability %age of normal P(K) (mm) Na [K] 20 400 100 4 [Na] 440 50 [C] 560 75 Chloride distribution Regulated Passive 1000.00 Done Familiarise yourself with the settings (hit any button you like - you can't cause any damage). The blue aquarium represents a tissue bath containing one cell (green) that is impaled by a recording electrode. You can set the temperature and external (bathing) concentrations of K-, Na-, and Cl-ions. In addition you can control the intracellular ion concentrations and set membrane permeabilities. Note that the permeabilities are relative to normal gk. 2. Which of these parameters would you expect to be able to control in a 'real' experiment? A7 K Eq-75.68 Graph CI Eq-50.79 Ion Concs FRIFFICE Na Eq 54.946 0 453 X
The line at the top of the screen shows the equilibrium potential for each ionic species and the resultant membrane potential. Reset Temp to 20ºC and Chloride distribution 'Regulated'. Focus on one ion species only (potassium). Because the program does not accept zero-concentrations, enter 1mM for [Na+] and [Cl], both outside and inside (you can type-in '1' or use the scrolling-arrows), also set the Relative permeability for Na and Cl to '0'. Note that the equilibrium potentials for Na and Cl now are 0-in effect, we now are dealing with a single ionic species. 2
3. Enter [K+] as indicated in the table. Predict the solutions to these conditions first, then verify by reading the Ex and MemPot. [K+]out [K+] in Ек Emembrane 20 20 0 0 200 20 58.176 58.176 400 20 75.688 75.688 800 40 75.688 75.688 20 400 -75.688 -75.688 to convince yourself that the equilibrium potential is determined by the ionic charge (z), set [K+]out and in to 1mM and gk to 1 and gNa to 100 [Na+]out [Na+]in ENa Emembrane -75.678 20 400 -75.688 and again, set [Na+]Jout and in to 1mm, gNa to 0 and gci to 100 [CI-]out [CI-]in Eci Emembrane 20 400 75.688 75.676 4. How do Ex and Em relate to the distribution of K-ions?
Now introduce a second ion species: sodium (ie. reset [Cl-]out and in to 1mM, gci to 0, and Chloride distribution to 'Regulated'). Enter the cat-ion concentrations as indicated in the table. Vary the Relative permeability, gx and gNa, as indicated in the table. [K+]out [K+] in [Na]out [Na+]in gk gNa Ек ENa Emembrane 20 400 440 50 100 100 -75.688 54.946 0.555 20 400 440 50 1000 1 -75.688 54.946 -75.142 20 400 440 50 10 1 5.6889 54.946 -46.615 20 400 440 50 1 10 5.6889 54.946 40.210 20 400 440 50 1 20 5.6889 54.946 46.502 20 400 440 50 2 40 5.6889 54.946 46.502 20 400 440 50 1 100 5.6889 54.946 53.013 205 400 440 50 20 10 -16.888 54.946 0 5. Where does the membrane potential settle, with gk >>gNa? And where with gk=gNa? How does the relative permeability (gk: gNa) influence the membrane potential? Find the external [K+] that will drive the membrane potential to zero (bottom row in table). 3
Return to more-or-less physiological conditions (as found in the squid giant axon, where many of these studies where performed - see picture of the startup screen, or simply exit and restart the program). From graph (b) on the right, estimate the relative permeabilities for Na and K. Then enter these relative permeabilities into the simulation, execute the simulation and read the membrane potential from the simulation. (Still with Cl-concentrations at 1mM and zero gci.) (a) +30 Membrane potential (mv) (b) Relative membrane permeability -70 600 300 50 1 O Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. παραστεί στις τοπικές ομοιότητα, και στους επισκέπτετε υπερήσει τότε που επιμετωπωπωπιεστές της του σπιτιού K+ C Na PNa 2 Time (ms) Gated Nat channel Gated K+ channel
time gk gNa Emembrane point 1 25 1 -59.865 2 25 25 0.5553 3 40 550 43.443 4 200 50 -29.174 5 300 1 -73.911 6 220 1 -73.295 7 25 1 -59.865 6. Confirm that the calculated membrane potentials more-or-less follow the shape of graph (a). So far, we have been neglecting the contribution of Cl-ions. Some cells have a Cl-pump, and the resulting uneven distribution of Cl-ions generates a Eçi that contributes to the membrane potential. Other cells lack this pump and the Cl-ions passively distribute themselves according to the electrogenic environment. Go back to 'squid' conditions. Investigate the relevance of regulated chloride distribution, as guided by the table. 5 لیا
Chloride distributi [CI-Jou [CI-]in ENa Ек Eci on Regulated 560 75 54.946 -75.688 -50.795 switch Chloride distribution to 'Passive' Passive 560 52 54.946 -75.688 -59.865 Passive 700 65 54.946 -75.688 -59.865 Passive 100 9 54.946 -75.688 -59.865 note that you cannot change the setting for [Cl]in (try it) switch Chloride distribution back to 'Regulated' Regulated 100 9 54.946 -75.688 -60.838 Regulated 560 9 54.946 -75.688 -104.38 7. What is the effect on Em of 'passive' versus 'actively' regulated Cl-ion concentration? Emembrane -55.976 -59.865 -59.865 -59.865 -59.961 -69.578
Again, start-off with 'squid' physiological conditions. Depolarise the membrane, by opening Na-channels (ie, increasing gNa to 200): (a) at a relatively low Cl-conductance (let's say 10% of gk) yes depolarisation (b) at a relatively high Cl-conductance (eg 500%). Not as easy to depolarise cell than low 8. What influence does Cl-conductance have on depolarisation? How does Cl-conductance control the cell's spiking threshold? What would be the physiological relevance of a neurotransmitter (such as GABA) opening Cl-channels at the post-synaptic membrane? Stayed negative because of the way it flows and the charge. Goes in negative charge so inside the cell is negative. Make call extra negative. The brain is the best, prescripber for anxiety, benzodiosapines (gaba a receptor) iron channel open lets chlorine in. The electrical behaviour of neurones is often studied using slices of brain tissue in vitro. It would be impossible to depolarise all neurons within that tissue preparation by electrical means. However, by changing the K+-concentration of the bathing medium, neurones can be depolarised en masse. 9. How? Investigate!
By manipulating the Nat-concentration of the physiological buffer, the nerve cells' sensitivities to depolarising stimuli can be altered. Investigate and explain. 10. Investigate and explain. Slow-K® is a depot preparation containing potassium. It slowly releases K+-ions and thereby restores and maintains adequate blood-potassium levels in individuals who suffer from hypokalemia. 11. What would happen if you crush the tablet and ingest it? How would the excitable cells in your body, eg the heart, respond? (Actually, the kidneys will rapidly excrete excess potassium, so things are not that lethal in practice)
Please help me answer these questions 3-11, Thank you!!
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Please help me answer these questions 3-11, Thank you!!
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