Week 11 Discussion Section Activity Nerve Potentials Student Version PDF

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Discussion Topic 11: Resting and Action Potentials Background readings: -Campbell Biology (11th Edition), Chapter 48, pp. 1065-1074 (please read in the eText on the course website) -Lecture 18

Introduction A neuron’s resting potential (RP) can be thought of as a battery for all electrical signal transmission that occurs in the nervous system. This negative membrane potential (inside relative to the outside) is created by the unequal distribution of different ion species across the membrane, the membrane permeability of these ions and an energy requiring ion pump. The Nernst and Goldman-Hodgkin-Katz (GHK) equations describe the membrane potential when it is dominated by single (Nernst) ion (K+) or when multiple (GHK) ion species contribute. The action potential (AP) is a brief electrical event that transmits signals within a neuron. It brought about by voltage and time dependent changes in the permeability of membrane voltage-gated Na+ and K+ channels, which pass their respective ions to support the AP current flow across the membrane. APs move information over long distances quickly down neuronal processes called axons. Two evolutionary innovations have arisen to enhance the spread of electricity down axons quickly: (1) myelination and (2) enlarged axon diameters. Myelination insulates the membrane to reduce current leak out of the axon, and large diameter axons provide a low resistance pathway for current flow down the axon. You will do two exercises today. In the first, you will use a computer simulation program to explore how the Nernst equation describes equilibrium potentials for a given ion (the balance between the electrical and chemical forces acting across the membrane on ions), and how the GFK equation describes the resting potential of neurons. In the second exercise, you will review action potentials and design activities to teach middle school students the membrane sequence of events that lead to generation of an action potential, and the physiological processes that enhance the speed of action potential conduction.

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Learning Concepts These exercises will reinforce the ideas of the generation and quantification of the resting membrane and the action potentials presented in Lectures 18. Exercise 1: 1. A neuron’s membrane potential is determined by the concentrations of different ion species in the intracellular and extracellular space, and the permeability of these ions through the membrane, especially potassium. 2. The Nernst equation describes the membrane potential when one ion dominates the membrane potential, e.g., if the membrane is only permeable to a single ion type. The Goldman-Hodgkin-Katz equation describes the membrane potential when multiple ions species contribute to the membrane potential 3. All electrical signaling transmission in and between neurons is a result of a change in the membrane potential caused by a change in ion permeability to specific ion species. 4. The action potential itself does not travel down the axon. The AP describes the voltage change in a local patch of membrane. As the voltage rises there due to Na+ inflow, passive spread of this voltage opens voltage-gated Na+ channels in the next patch of membrane and the AP regenerates itself there, which in turn opens channels in the next patch, and so on.

Exercise 2: 1. The waveform of the action potential consists of the following phases: rising phase (depolarizing), overshoot, falling phase (repolarizing), undershoot (hyperpolarizing). When the potential in a local patch of membrane changes from one phase to the next depends on voltage-dependent changes in sodium and potassium conductance. 2. The action potential is all or none: once triggered, every AP in a particular cell has the same amplitude and duration, because once the positive feedback loop is triggered, the amplitude and duration are fixed by the ion concentrations and ion channel distribution in that cell. 3. APs propagate without decrement along axons because an action potential at one location brings the neighboring regions to threshold, continuously regenerating the AP. 4. AP conduction along an axon can be sped up by myelination. Myelin, insulating layers of lipid bilayer of glial cells, increases the neuron membrane resistance so an AP can travel fast, without much decrement, over long distances. At intervals, a gap in the myelin (called a Node of Ranvier) which is loaded with voltage-gated Na+ and K+ channel, allows the AP to regenerate and regain its full amplitude. This winning combination of self-regenerating (slower) AP and (fast) passive propagation, called saltatory (“jumping”) conduction, allows for the fastest and longest-distance information transfer. 5. Instead of myelination, some neurons have axons with large diameters, which lower resistance along the axon and speeds up AP conduction. This, however, is not as effective as myelination in producing high speed AP conduction. Learning Objectives You will have learned this material when you can: Exercise 1: 1. Explain the difference between how the Nernst and the Goldman-Hodgkin-Katz equations describe the membrane potential and the relationship between them. Week 11 – Neural resting and action potentials

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2. Understand how an ion’s concentration inside and outside the cell, and it’s membrane permeability determine a neuron’s resting potential. 3. Understand that a combination of differing ion permeabilities can dynamically determine a neuron’s membrane potential. Exercise 2: 1. Describe how and when the membrane changes its permeability to specific ions during an action potential. 2. Understand how voltage gated Na+ and K+ channels open up to allow selective ion flow. 3. Explain why a large axon diameter facilitates AP propagation. 4. Explain how the “undershoot” phase of an AP promotes its unidirectional propagation.

Pre-lab questions and activity. You Must do this exercise before section and please bring your answers to section. Exercise 1: Nernst/Goldman Simulator -Go to the website http://www.nernstgoldman.physiology.arizona.edu/ and either open the simulator in your browser (“click launch now”) or download the application Part 1: Single Ions -Go to the “Nernst @37” tab and select “potassium.” Scroll the external and internal concentrations of potassium ion up and down. (Note that the sliders for internal and external concentrations have different scales—that’s just a quirk of the software.) 1. What happens to the membrane potential when the concentrations of K+ inside and out are equal? Why?

When they are equal the membrane potential of potassium goes to zero. This happens because usually potassium concentration is highe inside than outside of the cell. When adding more potassium outside of the cell to be equal then it lowers the normal resting potential so it’ll move to zero. Go to requlibrium +

2. What happens to the membrane potential when the concentration of K is 10 X higher inside the cell than outside? Explain this by the Nernst equation.

When increasing the concentration of potassium inside 10 times higher than the outside the membrane potential greatly increases, sinc in the Nernst equation, it measures the concentration of potassium outside of the cell over the concentration of potassium inside the ce -61.5 +

3. What is the Nernst equilibrium potential for K with the typical intracellular and extracellular neuronal concentrations of K+ shown in the table below? Adjust the concentration sliders to be as close as you can get to the values in the table, they don’t have to be exact. K+ equilibrium potential = -107.1 mV

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4. Increase the extracellular concentration of K+ stepwise as shown in the results of the experiment in the Figure below. Start with an inside K+ concentration of 124 mM/outside 3 mM, and increase the outside concentrations near to those shown in the Figure below (outside concentrations 3 to 120 mM K+). Write down the membrane potentials that result from each outside K+ concentration. Do the membrane potentials with greater outside K+ concentration follow the trend as in the Figure on the next page?

Outside Concentrations of K+ (mM) 3 10 40 80 100 120

Membrane Potential (mV - 99.4 - 67.2 - 30.2 - 11.7 - 5.7 - 0.9

Yes they follow the trend- as outside potassium concentration increases at each step increase, the membrane potential also becomes greater (less negative).

Figure shows the membrane potentials recorded from a neuron at different outside concentrations of K+ from 3 to 120 mM.

Part 2: multiple ions Go to the “Goldman @37” tab. 1. What is the difference between the Goldman and Nernst equations?

1. The Nernst equation looks at the ion concentrations, while the Goldman equation also looks at relative permeability and concentration gradient and is for multiple ions. 2. In the Goldman tab, keeping the ion concentrations at the default setting, change the permeability (e.g., PK+ for potassium (K+)) of each ion. a. What happens to the membrane potential when you increase the permeability of sodium? Of potassium? Of chloride? Increasing the permeability of sodium makes the membrane potential increase. Increasing the permeability of potassium makes the membrane potential decrease. Increasing the permeability of chloride makes the membrane potential decrease b. Write each observation down for each ion and explain why the membrane potential changed the way it did. The membrane potential changed since increasing Sodium: membrane potential becomes more positive. permeability means the sodium, potassium, and chloride Potassium: membrane potential becomes more negative. ions can easily move across the membrane so there’s less Chloride: membrane potential becomes more negative. buildup of potential across the membrane. Week 11 – Neural resting and action potentials

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3. Finally, starting with all intra- and extracellular ion concentrations of the Table below and permeabilities at zero, create a neuron that has a resting membrane potential of exactly -45 mV. You may change any permeability parameter you wish. Write down the ion concentrations and the permeability settings you chose.

Your settings for: 1645 PK+ _____________ ______ 2.25 [K+]out _______________ 124 [K+] in________________ 320 PNa+ ___________________ 109 [Na+]out _______________ 10.4 [Na+] in________________ 10 PCl- ___________________ 77.5 [Cl-]out _______________ 1.5 [Cl-] in________________ 4. How does the Goldman equation explain that despite the K+ dominance of the membrane potential a normal neuron’s resting potential is never at the Nernst Equilibrium potential for K+? The Goldman equation takes into account that different ions interact and affect the membrane potential altogether. If only K+ was affecting the membrane potential than the Nernst equation could be used. But in living cells there’s always more than one ion contributing to the membrane potential, which the Goldman equation accommodates.

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Exercise 2A: Action Potential Review Exercise (In-class Activity) Your TA will provide your group with a worksheet to review action potentials. Exercise 2B: Neurons in Action (In-class Activity) Your assignment here is to design a dynamic, creative way to illustrate to other students (could be college, high school, etc) how an AP works and how myelination and large axon diameter can speed up AP conduction. You can use any medium you can think of to use, like beads for ions, a theatrical description using the students to act out AP events or a way to graphically illustrate AP events. Use your imagination. Your TA will assign your group one of the following: 1. Portray the opening of voltage-gated Na+ and K+ channels in the proper sequence to depolarize from the resting potential and repolarize the AP back to the original resting potential. 2. Demonstrate how (1) myelination and (2) increased axon diameter increases AP conduction velocity 3. Demonstrate how the “undershoot” phase of an action potential (hyperpolarization following the falling phase) allows an action potential to be propagated in one direction down topic 2: an axon. The membrane initially becomes depolarized when voltage-gated sodium channels open in response to a stimulus, such as the binding of an inhibitory neurotransmitter in the dendrites. As the membrane potnetial has not yet depolarized to the threshold, this is considered a graded potential. With the remaining time, a group member will briefly report each group’s presentation idea to the whole section. Each presentation should begin with a brief description of the topic being demonstrated, followed by how this topic would be demonstrated to the middle/high school students.

Questions for discussion: 1. What do the expression “rubbing salt in a wound”, the lethal injection cocktail for convicted murder executions, Dr. Kvorkian’s suicide machine, hypokalemia and hyperkalemia have in common? 2. How fast is fast? What neurons do you think have the fastest AP conduction velocities (CV) in our nervous systems? Estimate how fast APs are travelling in these neurons and what physiological mechanisms support this fast conduction.

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Axon Alpha motor neurons

Diameter (micron ) 13-20

Myelin yes

CV (m/s) 80-120 (268 mph)

Gamma motor neurons

5-8

yes

4-24

Muscle spindle receptor

13-20

yes

80-120

Skin mechanoreceptors

6-12

yes

35-75

Fast pain

1-5

yes

3-30

Slow pain (C fiber)

0.2-1.5

no

0.5-2

Squid giant axon

500

no

19

Chara sp. (plant)

1000

no

0.4

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