Talk:Threshold potential

Introduction to Neuroscience Course Project

My name is Maggie Scollan and I am a junior at Boston College. As part of Dr. Joseph Burdo's Introduction to Neuroscience course, myself and others will be working to improve articles relating to the topic, in conjunction to the goals set out by the Society for Neuroscience. My group members are Marko Tkach and Nicole Kopidakis, and we will be expanding the information concerning Threshold Potential. For the next few days (November 2012), we will be in the process of editing this page, so ask that information is not deleted or edited without our knowledge. We are attempting to create an informative page with accurate information and appreciate outside edits, but want to be aware of edits made so that we can appropriately learn if there are mistakes. To further understand our purpose, click here for our project proposal. — Preceding unsigned comment added by Scollanm (talk • contribs) 01:06, November 3, 2012‎

November 3, 2012

Today, the following text was added to this page. The text is lacking citations as of right now within the text, but scholarly review articles on which all the text is written have been referenced at the bottom of the page. The goal is to have intext citations completed by next week. — Preceding unsigned comment added by Scollanm (talk • contribs) 01:06, November 3, 2012‎

I noticed the constructive criticisms regarding our citations and hyperlinks. As of today, I have gone through my section of the article [Discovery and the Characteristics of Threshold] and hyperlinked to other wikipedia sites so that our article is more directly connected within the encyclopedia. I also have added inline citations. - User:NicoleKopidakis —Preceding undated comment added 23:19, 3 November 2012 (UTC)

I too have gone through my section [Threshold Tracking Techniques] and added inline citations and hyperlinks to other wikipedia articles. Our next step as a group will be to add more External Links and perhaps a "See Also" section. - User:Scollanm —Preceding undated comment added 04:00, 5 November 2012 (UTC)

Let me suggest that you make the headings (titles) for each section with only the first word capitalized ("sentence case", not "title case"), as it says at MOS:HEAD. Also, the inline citations come after the period at the end of a sentence, not before, and there is no space before a citation begins. Also, please take a look at the edit I made about the reference citations, and see how to properly link the Notes to the References, also explained at Template:Sfn. --Tryptofish (talk) 19:36, 5 November 2012 (UTC)

Also visible in the page edit history. --Tryptofish (talk) 21:25, 3 November 2012 (UTC) The following discussion has been closed. Please do not modify it.

Discovering the Threshold Potential

Initial experiments revolved around the concept that any electrical change that is brought about in neurons must occur through the action of ions. Nernst applied this concept to discovering nervous excitability, and concluded that the local excitatory process through a semi-permeable membrane depends upon the ionic concentration. Also, ion concentration was shown to be the limiting factor in excitation. If the proper concentration of ions was attained, excitation would certainly occur. This was the basis off of which the threshold value was discovered.

Along with reconstructing the action potential in the 1950s, Hodgkin and Huxley were also able to experimentally determine the mechanism behind the threshold for excitation. Through use of voltage clamp techniques, they discovered that excitable tissues generally exhibit the phenomenon where a certain membrane potential must be reached in order to fire an action potential. Since the experiment yielded results through the observation of ionic conductance changes, Hodgkin and Huxley used these terms to discuss the threshold potential. They initially suggested that there must be a discontinuity in the conductance of either sodium or potassium, but in reality both conductances tended to vary smoothly along with the membrane potential.

They soon discovered that at threshold potential, the inward and outward currents were exactly equal and opposite. As opposed to the resting membrane potential, the threshold potential’s conditions exhibited a balance of currents that were unstable. Instability refers to the fact that any further depolarization activates even more voltage-gated sodium channels, and the incoming sodium depolarizing current will overcome the delayed outward current of potassium. At resting level, on the other hand, the potassium and sodium currents are equal and opposite in a stable manner, where a sudden, continuous flow of ions should not result. The basis is that at a certain level of depolarization, when the currents are equal and opposite in an unstable manner, any further entry of positive charge will generate an action potential.

Physiological Function and Characteristics of the Threshold

The threshold value controls whether or not the incoming stimuli are important enough to generate an action potential. Normal functioning of the central nervous system entails a summation of synaptic inputs made largely onto a neuron’s dendritic tree. These local graded potentials reach the axon initial segment and build until they manage to reach the threshold value. The larger the stimulus, the greater the depolarization, or attempt to reach threshold. The task of depolarization requires several key steps that rely on anatomical factors of the cell. The ion conductances involved depend on the membrane potential and also the time after the membrane potential changes.

The Resting Membrane Potential

The cell membrane, composed of a lipid bilayer, is highly impermeable to ions. Leak potassium channels allow for potassium to flow out of the cell along its concentration gradient. This is due to the high concentration of potassium within the cell relative to the outside. The sodium-potassium ATPase is an active transporter within the membrane that pumps potassium back into the cell and sodium outside of the cell, against their concentration gradients. This maintains the inside of the cell negative relative to the outside. The membrane also contains ion channels that are specific for sodium ions, however these remain closed in the resting phase. Therefore, the resting membrane potential value of about -70 mV lies closer to the equilibrium potential for potassium.

Depolarization

However, once a stimulus activates the voltage-gated sodium channels to open, positive sodium ions flood into the cell and the voltage increases. This process can also be initiated by ligand or neurotransmitter binding to a ligand-gated channel. More sodium is inside the cell relative to the outside, and the positive charge within the cell propels the fleeing of potassium through delayed-rectifier voltage gated potassium channels. Since the potassium channels within the cell membrane are delayed, any further entrance of sodium will activate more and more voltage-gated sodium channels. Depolarization above threshold results in an increase in the conductance of Na sufficient for inward sodium movement to swamp outward potassium movement immediately. If the influx of sodium ions fails to reach threshold, then sodium conductance will not increase a sufficient amount to override the resting potassium conductance. If successful, the sudden influx of positive charge will depolarize the membrane, and potassium will be delayed in re-establishing, or hyperpolarizing, the cell. Sodium influx depolarizes the cell in attempt to establish its own equilibrium potential (about +52 mV) to make the inside of the cell more positive relative to the outside.

Variations of the Threshold

The value of threshold can vary according to numerous factors. Changes in the ion conductances lead to either a raised or lowered value of threshold. Additionally, the diameter of the axon, density of voltage activated sodium channels, and properties of sodium channels within the axon all affect the threshold value. Hyperpolarization by the delayed-rectifyer potassium channels causes a relative refractory period that makes it much more difficult to reach threshold. This is because of the excess negativity in the cell, requiring an extremely large stimulus and resulting depolarization to cause a response.

Threshold Tracking Techniques

Threshold tracking techniques test nerve excitability, and depend on the properties of axonal membranes and sites of stimulation. They are extremely sensitive to the membrane potential and changes in this potential. These tests can measure and compare a control threshold (or resting threshold) to a threshold produced by a change in the environment, by a preceding single impulse, an impulse train, or a subthreshold current. Measuring changes in threshold can indicate changes in membrane potential, axonal properties, and/or the integrity of the myelin sheath.

Threshold tracking allows for the strength of a test stimulus to be adjusted by a computer in order to activate a defined fraction of the maximal nerve or muscle potential. A threshold tracking experiment consists of a 1-ms stimulus being applied to a nerve in regular intervals. The action potential is recorded downstream from the triggering impulse.The stimulus is automatically decreased in steps of a set percentage until the response falls below the target (generation of an action potential). Thereafter, the stimulus is stepped up or down depending on whether the previous response was lesser or greater than the target response until a resting (or control) threshold has been established. Nerve excitability can then be changed by altering the nerve environment or applying additional currents. Since the value of a single threshold current provides little valuable information because it varies within and between subjects, pairs of threshold measurements, comparing the control threshold to thresholds produced by refractoriness, supernormality, strength-duration time constant or “threshold electrotonus” are more useful in scientific and clinical study.

Requirements & Equipment for Threshold Tracking Experiments

The main requirements for threshold tracking are: 1) conventional EMG electrodes and a preamplifier for recording nerve or muscle action potentials, 2)an isolated, constant current stimulator and nonpolarizable electrodes, and 3) a threshold tracking apparatus, most usually a computer with QTRAC software. QTRAC software is a program which allows for total control of the output of current sources and includes: 1) a choice of tracking modes for determining the percentage size of the steps, 2) the ability to cycle between a number of stimulus channels, coordinating different conditioning + test stimuli for each and separating data recorded from each stimulus, 3) the option to set the amplitude of stimulus on one channel as the fraction of amplitude received by another channel, 4) the option to subtract and add responses to stimuli by different channels, and 4) options to adjust time increments so that they can be in regular steps, a specified irregular sequence, after a fixed number of test stimuli, or after a threshold has been determined to a specified accuracy.

Furthermore, tracking threshold techniques work best when either many units or only one unit are contributing to the target threshold response. If there are a few units, one abnormal or diseased unit could affect the average threshold value disproportionally and create results which inaccurately reflect the nature of the nerve(s).

Threshold Electrotonus

A specific threshold tracking technique is “threshold electrotonus,” which uses the threshold tracking set-up to produce long-lasting subthreshold depolarizing or hyperpolarizing currents within a membrane. Threshold decrease is evident during extensive depolarization, and threshold increase is evident with extensive hyperpolarization. With hyperpolarization, there is an increase in the resistance of the internodal membrane due to closure of potassium channels, and the resulting plot “fans out.” Depolarization produces has the opposite effect, activating potassium channels, producing a plot that “fans in.”

Advantages of Threshold Tracking Techniques

Tracking threshold has advantages over other electrophysiological techniques, like the constant stimulus method. This technique can track threshold changes within a dynamic range of 200% and in general give more insight into axonal properties than other tests. Also, this technique allows for changes in threshold to be given a quantitative value, which when mathematically converted into a percentage, can be used to compare single fiber and multifiber preparations, different neuronal sites, and nerve excitability in different species.

References

Bostock, H et. al. 1997. Threshold Tracking Techniques in the study of Human Peripheral Nerves. Muscle & Nerve. 21: 137-158.

Burke, D, et. al. 2001. Excitability of human axons. Clinical Neuropysiology: 112: 1575-1585.

Nicholls, J. G., Martin, A. R., Fuchs, P. A., Brown, D. A., Diamond, M. E., & Weisblat, D. A. (2012). From neuron to brain. (5 ed.). Sunderland, MA: Sinauer Associates, Inc.

Rushton, W. A. H. (1927). The effect upon the threshold for nervous excitation of the length of nerve exposed, and the angle between current and nerve. The journal of physiology, 63(4), 357-377.

Stuart, G. (1997). Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends in neurosciences, 20,3, 125-131. <http://www.le.ac.uk/users/cd133/4.pdf>.

Trautwein, W. (1963). “Generation and conduction of impulses in the heart as affected by drugs.” Pharmalogical reveiws, 15(2), 277-332.

Peer Review for BI481

Overall, this article covers a lot of the information necessary in understanding the threshold potential and it seems to be structured very well. However, there are a few changes that I believe would enhance the article even further. First of all, the introduction seems to be a little to specific, as well as brief. I think that instead of listing specific threshold potentials in the introduction, move those facts to a later section, either Discovery or Physiological Function, and in its place, sum up the articles contents more thoroughly. The introduction should serve to outline what is going to be stated in the article, as well as any other general facts about the threshold potential instead of such detailed information. Also, in the third paragraph under the Discovery heading, in the first sentence, it would be helpful to explain exactly which currents are equal and opposite, those being the Na and K currents. Even though it may be implied, it would be more easily understood if those were labeled explicitly. Although the Physiological Function section has a great breakdown of the information and structure, it would serve the reader better if the variations section had more detailed explanations of how exactly the variables discussed affect the threshold potential, rather than just stating that they do. Lastly, I think that images of the plots described in the Threshold electrotonus section ("fans out" and "fans in") would be very helpful in understanding the exact results received in such experiments. If these changes were made to the article, I believe that it would be a very great article with a lot of very useful and interesting information.Schererp (talk) 06:00, 19 November 2012 (UTC)

I think this article does a good job in describing the main points necessary to understand the concept of the threshold potential. However, this paper does have several flaws. Several of the grammatical errors get in the way of understanding the information, and some of the cross citing within Wikipedia seems to be either unnecessary and gets in the way of understand the material. For instance, “Therefore, resting ion channel for sodium will depolarize and thus excite, while channels for potassium or chloride will hyperpolarize and thus inhibit.” In this sentence, the way that “resting ion channel” is linked causes a grammatical error, which causes some confusion. Some of the subjects need further explanation (Threshold Electrotonus, for example) and analysis. The citations seem repetitive in the reference section- if you look at other pages there is a format that seems to work and is pretty good at consolidating them. Additionally, some of the phrasing is informal (for example, using Nernst’s last name instead of his full name). The information is very obvious in this article, and the research that was done was pretty good, however I think the information would be best presented if some of these changes are made. Bonnerry (talk) 04:02, 19 November 2012 (UTC)

This article does a good job of defining the threshold potential and outlining it's significance in the normal firing of an action potential. Although it was mentioned briefly, I think the article could be improved by a more in depth discussion centered around variations in threshold potential. It was mentioned briefly in the variations section that the threshold potential can change (changes in ion conductance, axon diameter, etc were given as reasons) but there wasn't too much mentioned in terms of what this actually means in the bigger picture. I think it would be really interesting to get more in depth with the clinical significance of this (I know the cardiovascular system was mentioned briefly, but there are many other systems and responses that are greatly affected by having a lower (or higher) threshold potential. A detailed discussion of how our body reacts to different situations and how the threshold potential is changed would add a lot of depth to the article. It could also be beneficial to mention any genetic causes that can affect threshold potential and if there have been any recent discoveries made (or where future research could be focused in regards to the threshold potential). Coburnt (talk) 03:00, 17 November 2012 (UTC)

Your article is well-written and maintains a neutral, informative tone throughout. You did a good job of explaining thoroughly the threshold potential by including all the mechanisms that come into play to get the cell to this value. A few things you could add to improve the article could be a short explanation, or a hyperlink, of what exactly is a delayed rectifier current. We know plenty about it because of class, but I'm not sure if all readers would be able to understand what it is without the Neuroscience background. Also, when you mention the sodium potassium pump, I think it would be good to add the specific ratio of Na and K getting pumped in and out so you have more specificity in your article. Lastly, like the comment above mentions, it would add a lot of depth to the article to talk about how the variations in threshold potential actually affect the cell. Susana.benitez (talk) 19:20, 17 November 2012 (UTC)

Hi, I think you present a good deal of information in this article, and I hope you find my comments below helpful:

Your introduction section is concise and to the point, but I think some rewording will help to make it a bit clearer and more grammatically correct. For instance, the sentence “If ion channels are available, that will move the potential in the direction of the equilibrium potential for that ion:” could be reworded to read “If ion channels are present in the membrane, the potential will be shifted in the direction of the equilibrium potential for the particular ions that flow through the channels.” Do you have any journal articles or textbook information that backs up this assertion and could be cited here? Also, when you say “potential” in this sentence are you referring to the membrane potential or the threshold potential? Based on class discussion, I think the equilibrium potential of the ions involved affects the resting membrane potential, but you may want to clarify how it affects your topic, the threshold potential. Secondly, instead of saying that “Na+ is approximately +55mV”, you may want to write that the “equilibrium potential for Na+ is approximately +55mV.” Given that equilibrium potential is dependent upon ion concentration, you may want to also include a caveat that these numbers are variable.

Also, under “Physiological function and characteristics,” you mention that “The threshold value controls whether or not the incoming stimuli are important enough to generate an action potential. … These local graded potentials reach the axon initial segment and build until they manage to reach the threshold value.[4] The larger the stimulus, the greater the depolarization, or attempt to reach threshold.” (1) I’m not sure that “important” is the best word to use here - "sufficient" or "excitatory" might be better options; and (2) can’t some stimuli be inhibitory? Large inhibitory stimuli would not lead to the firing of an action potential, making the last sentence quoted above false. The summation of IPSPs and EPSPs determines whether or not the cell fires, so it is possible that the graded potentials don’t manage to reach threshold. Also, the axon initial segment is associated with the axon hillock – including a link to the Wiki page for the axon hillock may be helpful for readers.

Lastly, several of your external links listed at the bottom of the article are broken or don’t seem to redirect the reader to information regarding your topic. RNewmiller (talk) 21:09, 18 November 2012 (UTC)

In the introduction, I think it is worth mentioning the significance of the threshold potential in the propagation of signaling throughout the CNS and PNS. And perhaps even, just briefly, mention that propagation of an action potential can be achieved chemically or electrically. Information about specific equilibrium potentials may be better suited for a different part of the article, which discusses in detail electrical propagation down the axon. You can’t be sure of the levels of preexisting knowledge of your readers, so I think it’s best to err on the side of simplicity.

I thought the DISCOVERY section was well done and helpful. However, in the first few sentences of the PHYSIOLOGICAL FUNCTION section you mention local graded potentials without any introduction or hyperlink. Explaining the origins of these potentials—perhaps just citing external stimuli as commonly associated with local graded potentials.

Otherwise, I thought the whole article was very well organized and contained some really useful information. On the whole, I thought it flowed together very naturally and will be helpful for those seeking more detailed information on the subject. James Kaberna (talk) 18:20 19 November 2012 —Preceding undated comment added 23:19, 19 November 2012 (UTC)

I think that the article is good for the basic understanding of the threshold potential. The discovery section is a good introduction to the topic. The function and characteristics part is pretty good, except I feel that it is not explained how the resting membrane potential and depolarization relate to the threshold potential. I also think that it would be good to say the importance of reaching threshold potential and what would happen if threshold potential is not able to be reached. Overall, good page though. — Preceding unsigned comment added by 136.167.196.17 (talk) 04:19, 20 November 2012 (UTC)

Overall, this article is very informative and illustrates the function of threshold potentials very well. Having said this, I believe some small improvements could really help the article become even better. Firstly, the paragraph titled “Threshold Electronus” seems somewhat ambiguous in its goal. Although it is obviously an important tracking technique, the significance of what it means is lost without a good sentence or two describing how it can help in understanding threshold potentials. A short sentence leading off the section describing the functionality and gains of the technique could go far into attributing more meaning for the topic in the article. Also, there is a small typo at the end of the section “Threshold Electronus”, where it seems that two words are used for the same function in the sentence.

Additionally, I would say that the “Advantages” subheading is wasted at the end of the “Tracking Techniques” section. I believe that this would be far more valuable integrated at the beginning of the section. It would also fit in very nicely in this area if it were a bit more structured. There is a large amount of information here and it would serve its purpose better if it were combined with the information from the “Advantages” subheading, and developed into new subheadings to help guide the reader. Finally, I feel that the paper could be improved upon if the section titled “Clinical Significance” could be expanded somewhat. It seems as though there might be more out there on such important medical conditions such as arrythmia, and that there might even be more in the five different papers you sited. najabouarraj (talk) 23:45, 19 November (UTC)

Review

Good job so far. I noticed a few proofreading/wording errors: the omission of units (-70 mV) and the unnecessary use of a comma in the last sentence of the introduction. Also, the beginning of the second paragraph states: “The threshold potential is simply a specific measurement of the difference in charge across a cellular membrane.” However, this describes any membrane potential, not specifically a threshold potential so you should revise this sentence. Next, when you introduce Nernst for the first time in the “Discovery” section, include his first name. You should also correct the disambiguation needed tags in the “Discovery section.” Also, I would like to see an elaboration of the causes of threshold variation in the “Variations” section. In particular, you could give an example of a specific type of neuron with a large axon diameter and its threshold value. You could also briefly list mechanisms for the change in ion conductances that bring about changes in the threshold value, e.g. toxins and the problems that arise from toxins. Overall, nice work!-Reedich (talk) 19:31, 29 November 2012 (UTC)

Response to Reviews

After reading the numerous peer reviews and constructive criticisms on the Wikipedia page, I made changes to the body of the article in order to improve it. I added full names to the scientists who performed the experiments, so that they were less ambiguous. Additionally, I fixed any grammatical errors that were present and parts of the article that were deemed unclear. Most importantly, I added more examples of the variations in threshold potential. This was important to discuss that topic in more depth, which was a recurring comment mentioned in the peer reviews. Overall, the discovery and physiological function sections were improved so that they provided more examples and better explanations. NicoleKopidakis (talk) —Preceding undated comment added 22:59, 1 December 2012 (UTC)

I first attempted to rework the intro so that it would read more clearly. In my section, Tracking Techniques, I eliminated the Advantages section and added it to the introductory paragraphs of the topic, thinking that it made more sense there and there was not enough information in the section for it to stand on its own. The Threshold Electrotonus section was also reworded and added to. Pictures could not be added of the "fanning in" and "fanning out" plots because there were no pictures available of those occurrences in Wikipedia commons. Scollanm (talk) 17:53, 2 December 2012 (UTC)

Marko's Response

I expanded the "clinical significance" section, incorporating conditions of both the nervous and cardiovascular systems. Citations are included as necessary.

Marko Tkach (talk) 05:10, 3 December 2012 (UTC)

Threshold potential value range (Intro, 2nd paragraph)

Speaking as the person who added the "citation needed" in June 16, I think we can do better than Khan academy. While it's an excellent resource for learning, it's not a proper source. Surely we can find a first-hand reference (and yes, I have been looking). I wouldn't be surprised if Khan academy got their info from this article in the first place... — Preceding unsigned comment added by 145.107.112.139 (talk) 13:45, 27 January 2017 (UTC)

I agree, and I replaced it with a better source. --Tryptofish (talk) 01:52, 28 January 2017 (UTC)

What actually CAUSES the threshold potential to BE the value it is?

I find this to be a nicely written article, thank you! But I'm thinking that it could be interesting/useful to include whatever it is that causes the value of the threshold potential to be what it is. I'm not talking about things which can assist or impede REACHING that threshold value, but rather what is it that causes the threshold value to BE the value it is in the first place. I'm thinking it might/must relate to something like the 'springiness' of the voltage sensor/gate, that is, how much of a voltage is necessary to overcome the resistance of the voltage sensor to MOVE (polar strength of the sensor? or shape connections to rest of pore?) and thus either move itself out of the way for ions to pass through the pore (if it's a gate), or to re-configure the shape of the pore to allow ions through (whichever is the way the voltage sensor relates to ions passing through). Is the cause of the value of the threshold anything like that, or what? UnderEducatedGeezer (talk) —Preceding undated comment added 02:04, 10 April 2017 (UTC)

Reference issue

Seifter 2005, p. 55. seems to be broken. Can someone hyperlink this? — Preceding unsigned comment added by 76.122.189.89 (talk) 19:21, 9 December 2019 (UTC)