Talk:Voltage-gated ion channel

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The

The individual types of voltage gated ion channels have a bigger write up than this page and they both go into greater depth than a newbie would be interested in. This page should probably be used to give a broad introduction to them, their importance to the generation of action potentials and heart rhythms. Discussions of their locations on basal dendrites and spine heads would be worthwhile. Perhaps a discussion of related mathematics and how adding various channels can push limit cycles and bifurcations around the phase space.--Andorin (talk) 18:02, 27 February 2008 (UTC)

I

I quote:

"They have a minor role in excitable neuronal and muscle tissues"

What ridiculous kind of misleading statement is that? They are fundamental to the workings of neurons and minor variations in their type and location can result in entirely differant qualitative effects. --134.225.184.116 (talk) 17:54, 27 February 2008 (UTC)

Normally, I'd invite you to be bold and fix it yourself, but I've already reverted it to the previous information. It appears to have been the victim of a newbie editor. WhatamIdoing (talk) 06:50, 8 March 2008 (UTC)

Where do the ions come from?

After reading this page, it's not so clear to me where the ions come from. They are coming through the channels on the membrane that can be opened/closed by certain mechanisms... but who is sending/generating them? Is this another inter-Neuron connection apart from the dendrites/synapses? (I am not a biologist, so please excuse my lack of proper terminology) 134.100.6.103 (talk) 18:30, 23 May 2008 (UTC)

open and closed by depolarization

can someone clarify in the article if it is both opened by depolarization and closed by depolarization (in nerves?). Thanks. 207.151.245.45 (talk) 17:29, 23 July 2008 (UTC)

Simple English

Could someone with expertise in this please create a simple english page for this article? Thank you — Preceding unsigned comment added by Mbb1056 (talk • contribs) 17:37, 29 March 2014 (UTC)

Plants, DACs and HACs

Plants aren't mentioned, but of course they too have voltage-activated channels. The article makes it sound like all such channels are activated by depolarization. A DAC is a depolarization activated channel, and HAC a hyper polarization activated one.Tedtoal (talk) 07:25, 29 October 2014 (UTC)

I added an example of hyperpolarization activation. --Tryptofish (talk) 21:50, 29 October 2014 (UTC)

Plans for Proposed Changes

Hello! I am planning to make some significant additions to this article and would like to know other people's thoughts on what I plan to add.

Proposed Changes for Voltage-Gated Ion Channels:

• Per article talk page, make language less technical to improve understanding in non-science users
• Expand on the overview section of the article, giving a clear basic summary of the implications of voltage-gated ion channels
• Expand on the protein structure of voltage-gated ion channels and how it relates to their functionality
• Give comprehensive overview of the mechanisms of voltage-gated ion channels and how they allow ions to pass through biological membranes
• Give brief summary of some ways in which voltage-gated ion channels can malfunction related to human disease

Please let me know if there is anything else you would like to see changed about this article, or if you have any concerns about what I plan to add. Thank you! — Preceding unsigned comment added by Efazzari (talk • contribs) 16:05, 2 February 2016 (UTC)

Great! I look forward to watching the article improve. Looie496 (talk) 17:23, 2 February 2016 (UTC)

Classification

About this. Well, as far as I remember, TCDB provides an official classification of TM transporters approved by International Union of Biochemistry and Molecular Biology. My very best wishes (talk) 02:22, 25 April 2016 (UTC)

What does that approval consist of? What is the process, and who makes the decision? --Tryptofish (talk) 20:14, 25 April 2016 (UTC)

It seems to me that IUBMB treats this classification: [1], as being primary over this: [2]. --Tryptofish (talk) 22:02, 25 April 2016 (UTC)

And in fact, [3] is not the same at all as what was edited here. --Tryptofish (talk) 22:18, 25 April 2016 (UTC)

Yes, you are right. These versions of classification are partly different. That's why this version was correct version: it provides in-line referencing to support classification included to the page. It is also important that if we claim on the page: "this is a classification of proteins according to TCDB", that should indeed be classification of proteins according to TCDB, that is according to the most recent version of TCDB classification. Look, this is just a standard/common situation with classifications of proteins: all of them (including Pfam, InterPro, etc.) are constantly updated. Same with any biological classifications, including species. My very best wishes (talk) 15:06, 26 April 2016 (UTC)

@My very best wishes: Whatever else may be the case, your unilateral removal of the undue weight tag is contrary to policy and is disruptive. Please do not ever do that again. --Tryptofish (talk) 21:26, 26 April 2016 (UTC)

Now as to the content, you appear to be saying that there are multiple classification systems in the source material, with TCDB being just one of them. In that case, WP:DUE requires us to present TCDB as just one of several, rather than as the only one. According to TCDB, the K⁺ transporters are abbreviated as "Trk". However, Trk is very widely recognized as the abbreviation, instead, for tyrosine receptor kinases. This is a specific concern that makes me doubt that what is currently on the page has really been well-vetted by peer review. --Tryptofish (talk) 21:43, 26 April 2016 (UTC)

So, do you agree that except tagging this version was basically correct version with respect to providing inline references and correct/current rather than outdated TCDB numbers? Tagging is a minor thing. I usually do not even care to argue about it. As about other classification systems, yes anyone can include them, although they are usually similar to TCDB families. If you know them, please go ahead and include. My very best wishes (talk) 22:12, 26 April 2016 (UTC)

No, I don't agree with that, not even close. If there are multiple systems of classification in the source material, then it violates WP:NPOV to present a single one of them as though it were the only one – and violating NPOV is far from a "minor thing". --Tryptofish (talk) 22:31, 26 April 2016 (UTC)

Nor is it typical of most systems to use "TrK" in that way. --Tryptofish (talk) 22:34, 26 April 2016 (UTC)

OK, I agree with you: there is an WP:NPOV problem. How to fix it? Here is my suggestion using TrK as an example. My very best wishes (talk) 18:18, 27 April 2016 (UTC)

I think that, instead of having a section named Classification or Nomenclature (after all, Voltage-gated ion channel#Different types is really more to the point as to classifying different kinds of voltage-gated ion channels), it would be better to rewrite the section in terms of phylogeny, and to format it as paragraph text instead of as a list. After all, that is what the source material is really about: how different kinds of membrane proteins of various channel or transporter types are homologous to, and therefore evolutionarily related to, the actual voltage-gated ion channels. The more I try to make sense of the current content, the more it seems to me that the VIC "family" is a member of the VIC "superfamily". Thus, what the TCDB calls "TC# 1.A.1" are the voltage-gated ion channels, the subjects of this page. On the other hand, "TC# 1.A.2" and higher are related members of the "superfamily", but are not voltage-gated ion channels themselves. It would be very useful to indicate on this page how these various molecules are related to one another evolutionarily, but it is either misleading or WP:UNDUE to present them as being the various kinds of voltage-gated ion channels. --Tryptofish (talk) 00:10, 28 April 2016 (UTC)

You probably think that TCDB is something similar to Enzyme Classification, as actually claimed in a number of sources, i.e. a purely function-based classification. Fortunately, this not at all the case. For example this family includes receptors and pumps. Actually, these proteins were classified first into families and superfamilies based on their phylogeny (sequence alignments), and then these families were combined to classes based on their function. That's why the families are rather similar in TCDB and phylogeny-based systems like Pfam, InterPro and Uniprot, although I am not telling they are exactly identical. I remember only one classification of TM proteins which is really function-based, that one. In a number of cases it combines completely evolutionary unrelated proteins in the same family. Authors of TCDB knew better. My very best wishes (talk) 02:34, 28 April 2016 (UTC)

Strange. (Did you just say that "a number of sources" are wrong according to you?) No, I think that TCDB is very far from being function-based. Ion channels and ion transporters are two different things, functionally and mechanistically. But I think that it is useful to have this page cover the phylogenetic similarities. --Tryptofish (talk) 00:44, 29 April 2016 (UTC)

As about "strange", yes, I was not clear enough. Actually, sources tell this is a "mixed" phylogenesis/function based system. I only clarified above what it means. My very best wishes (talk) 12:27, 29 April 2016 (UTC)

All protein families currently on this page are evolutionary related. Thank you and good luck with improving these pages! My very best wishes (talk) 03:58, 29 April 2016 (UTC)

• In the next couple of days, I'm going to rewrite the "Nomenclature" section in term of phylogeny, as I described a few comments above. We have reliable sourcing that these things are phylogenetic relationships, but the supposed "classification" is clearly misleading, and multiple editors are now saying so. --Tryptofish (talk) 21:29, 5 May 2016 (UTC)

But this section is already written in terms of phylogeny because the families have been derived based on multiple sequence alignments. In addition, it is commonly accepted that 3D structures of the proteins and biological functions can be used as additional, but frequently important information in creating such classifications that are to a certain degree subjective. Yes, this particular classification was suggested by TCDB authors, however an independent classification, i.e. Ion channel family is rather close to that one. There are also some other classifications, such as one provided by Structural Classification of Proteins database, etc. If you are going to describe and compare what they all provide for this group of proteins on the page (there are certain differences in these classifications), this is obviously fine per WP:NPOV - I agree. My very best wishes (talk) 16:24, 6 May 2016 (UTC)

Incorrect deletion

Given that sub-page Voltage-gated ion channel (VIC) family (TC# 1.A.1) of this page has been now incorrectly deleted, I would like to ask: To which family human proteins KCNA1; KCNA2; KCNA3; KCNA4; KCNA5; KCNA6; KCNA7; KCNA10 and a lot of others belong?! Please see page Ion channel family that possibly should be merged with this page. My very best wishes (talk) 00:03, 2 May 2016 (UTC)

The AfD decision reflected consensus, and you would do well to accept that. (If you don't, you can ask the deleting administrator at his talk page, and then go to WP:Deletion review. But I very much doubt that you will get a different outcome.) If there is any kind of merge, it should be a merge of the "family" page into this one, and not the other way around. As for your question about the KCNAs, for Wikipedia's purposes, it depends upon which source one is citing. --Tryptofish (talk) 01:03, 2 May 2016 (UTC)

Who cares?. I can only hope that you and others who commented on the AfD will improve these pages. What happens is that people who actually know the subject, care about it and improve these pages (like Transporter Guy) are getting ostracized on wrong grounds, such as having "COI". I can easily agree that COI is a huge problem for pages on political subjects where people are paid to promote propaganda. However, this is usually not a big deal for pages on scientific subjects (yes, I saw some examples on COI talk page, but they are obvious and different from this case).My very best wishes (talk) 16:12, 2 May 2016 (UTC)

I am normally loathe to refer to anything pertaining to who am in real life by way of demonstrating my "qualifications" as an editor, because I believe strongly in the Wikipedia ethos that anyone can edit. However, your comment makes me feel the need to point out that, in real life, I have been a long-time tenured professor at a large US research university, with an expertise in ion channels. I know about the subject and care about it, and I am an editor because I do indeed want to improve pages. I also never said that you have a COI, just that you are wrong on the merits. --Tryptofish (talk) 21:59, 2 May 2016 (UTC)

If you have an expertise in this area, why did you just make this edit? Do not you know that some proteins from this family, in particular famous KcsA potassium channel, are not activated by TM potential, but by pH changes? This is classic work by MacKinnon he received Nobel prize for. To be activated by TM potential, KcsA must have famous voltage sensor domain, something it does not have. There is no question that KcsA belongs to this family. This is according to every classification because the structures of the channels are superimposamble and there is sequence homology. Please explain where I am wrong. I am not an expert in ion channels. My very best wishes (talk) 02:52, 3 May 2016 (UTC)

Voltage-gated ion channels are: voltage-gated. KcsA is an ion channel that is structurally homologous to the voltage-gated ion channels, so in a structural sense, an amino-acid sequence sense, it is "related". That does not mean that it is functionally or mechanistically related. What you say "there is no question" about is actually just a matter of structure, of sequence, not a matter of function or mechanism. KcsA is gated by pH. Voltage and pH are obviously two different things. So KcsA is not voltage-gated. Because it is an ion channel that is not voltage-gated, it is not a voltage-gated ion channel. Again: voltage-gated ion channels are voltage-gated. By definition. (And MacKinnon, whom I know personally, won the Nobel for the crystal structure, not for determining the gating mechanism.) If you want to make Wikipedia say that ion channels that are not voltage-gated are "voltage-gated ion channels", you are incorrect and I will oppose you on that. But saying that these other ion channels are phylogenetically related to the voltage-gated ion channels is entirely appropriate. --Tryptofish (talk) 20:55, 3 May 2016 (UTC)

Oh no, KcsA belongs to this group of proteins. This group of proteins was called "voltage-gated channels" because most of them are voltage-gated channels, not because all of them are voltage-gated. Same with naming other protein families. If you are making a WP page about foxes, this should be a page about foxes according to the existing biological classification - as defined in RS, not according to opinion of a wikipedian. Same about pages that describe protein (super)families, and this is one of them. There is huge literature telling that KcsA potassium channel belongs to this group of proteins, but it is easier to look at the internet resources. UniProt: here is KcsA, and it belongs to the family of potassium channels, most of which are voltage-gated. Pfam: yes, it belongs to this family which belongs to this superfamily. TCDB - yes, sure. Here is the question: can you show me any other well known classification which tells that KcsA does not belong to this group of proteins? My very best wishes (talk) 22:35, 3 May 2016 (UTC)

Nonsense. You are defining "belongs to this group of proteins" as belonging to groups defined by sequence homology. Of course websites for databases that are based on sequence homology are going to show that. --Tryptofish (talk) 22:42, 3 May 2016 (UTC)

Yes, sure, which proteins belong to the same group depends on their sequence homology. This is widely accepted approach, just as biological classification of foxes or whatever. The resources above and sources (not me) tell that KcsA belongs to the (super)family of Voltage-gated ion channels, which is the subject of this page. We are not talking here about any channels that are potential-dependent, right? (because then one would have to include mechanosensitive channels, and a lot of other potential-sensitive systems). Can you show me any RS or resources which tell that KcsA does not belong to this group of proteins? My very best wishes (talk) 23:00, 3 May 2016 (UTC)

Indeed, we are not talking about any channels that show responses to potential. After all, KcsA is weakly voltage-sensitive. And I am not disagreeing with you in any way with respect to homology. But a very authoritative secondary source is Bertil Hille's book on ion channels: [4]. Chapter 3 of the book is titled "The superfamily of voltage-gated channels", and throughout it, he treats "voltage-gated" as being voltage-gated. On page 81, he has a subsection of the chapter in which he discusses the idea of "superfamily", and his discussion is in terms of sequence homology. But later in the book, on page 155, he discusses how "The bacterial KcsA channel is much like eukaryotic K channels". In this subsection he describes KcsA, and here is his concluding paragraph: "In all these respects, the conducting pore of KcsA is an excellent model of eukaryotic K channels, although its gating is apparently not like the channels we have discussed so far. The most reliable way to open the KcsA channel is to lower pH on the intracellular side. Channel opening also has a weak voltage dependence. In brief, the selectivity filter and vestibules of the KcsA structure should give a reliable idea of K-channel architecture. The other details may not be general." After discussing "the superfamily of voltage-gated channels", he says of KcsA that "its gating is apparently not like the channels we have discussed so far". That's what he says, verbatim, and it's what I have been saying all along. --Tryptofish (talk) 23:31, 3 May 2016 (UTC)

That's exactly what I am talking about. In this book KcsA appears in a chapter dedicated to voltage-gated channels - as a protein evolutionary related to other members of this group, except it obviously has no voltage sensor. That's how it should also be included on this page. My very best wishes (talk) 23:49, 3 May 2016 (UTC)

No, it's not in the chapter about voltage-gated channels; sorry if I didn't make that clear enough. Page 155 is in a much later chapter, about K and Cl channels, both voltage-gated and otherwise. And what he actually says about KcsA makes it very clear that (1) it is homologous to, and an excellent structural model for, the conducting pores of voltage-gated channels, and (2) it is not gated like the voltage-gated channels and is not useful as a model for their gating. --Tryptofish (talk) 23:56, 3 May 2016 (UTC)

Aside from parsing KcsA, there is a bigger picture here. This page is about Voltage-gated ion channels. As such, it is about ion channels that are voltage-gated – not about ion channels that are not voltage-gated, and not about membrane proteins that are not ion channels. If you don't agree with me, I suppose you can try an RfC, or employ some other way of seeking opinions from more editors. --Tryptofish (talk) 00:19, 4 May 2016 (UTC)

The definition of voltage gated ion channels should be based on function/mechanism and not sequence homology. It confuses readers to present conflicting definitions. Hence I think this edit was entirely appropriate. Furthermore, to eliminate conflict between sequence and function, it would make far more sense to list KcsA along with KCNA1, KCNA2, etc. in the potassium channel article, than here. This is yet another example where the TCDB classification is deficient. Boghog (talk) 07:09, 5 May 2016 (UTC)

Obviously, it also belongs to page potassium channel. Sure, I agree to emphasize main function of this protein family in intro. This is still a page about protein (super)family, is not it? Two more questions:

1. What do you think about the relationship between proteins described on this page and Ion channel family? I thought they are basically the same. Would it be reasonable to merge content from Ion channel family into this page?
2. What do you mean by telling "TCDB classification is deficient"? I am not sure. Any RS telling that "TCDB classification is deficient"? To my knowledge, this particular superfamily in TCDB was chosen essentially in the same manner as in Pfam and other classifications (hence the possible merging with page Ion channel family). My very best wishes (talk) 16:33, 5 May 2016 (UTC)

Hello!

Hi, my name is Jarett Anderson and I am a student studying biophysics at Brigham Young University. I would like to edit this article to add some detail, I thought about adding the possibility that sodium channels developed, and as a result of this, calcium ions would be able to be used as signaling molecules instead of depolarizing the membrane? Obviously, I would do a fair amount of research and cite the authors as I used my own wording to insert the information, but does anyone believe that this article could benefit from having this information?

Thanks!

Jarett.anderson (talk) 03:32, 11 October 2017 (UTC)

Hello, and welcome to Wikipedia! And thank you for asking for advice here. I think that the process of sodium current-mediation of calcium current activation, leading in turn to second messenger-like effects of intracellular calcium ions could be a good topic here, subject to due weight. You would of course need to carefully support the content with reliable sources. (Also please be aware that some calcium currents activate at lower membrane potentials than sodium channels do, so sometimes it's calcium that leads to sodium, rather than the other way around.) In addition, you ought to consider how much information is appropriate for this page, about ion channels, as opposed to other pages that deal separately with intracellular signaling. Also, you have a very good resource for advice in Ian from Wiki-Ed.

I hope that you will WP:BEBOLD and feel free to add some content, while also keeping in mind that other editors will be free to change anything that you write. Also, it is helpful if you not add a lot of content all at once, because that makes it harder for other editors. You can also put proposed text here on the talk page, and ask for editor feedback before moving it to the actual page. Happy editing! --Tryptofish (talk) 17:03, 11 October 2017 (UTC)

Marban, Eduardo, et al. “Structure and Function of Voltage‐Gated Sodium Channels.” The Journal of Physiology, Blackwell Science Ltd, 22 Sept. 2004, onlinelibrary.wiley.com/doi/10.1111/j.1469-7793.1998.647bp.x/full.

Bouza, A A, and L L Isom. “Voltage-Gated Sodium Channel β Subunits and Their Related Diseases.” Handbook of Experimental Pharmacology., U.S. National Library of Medicine, 1 Oct. 2017, www.ncbi.nlm.nih.gov/pubmed/28965169.

Sato, C, and G Matsumoto. “Sodium Channel Functioning Based on an Octagonal Structure Model.” The Journal of Membrane Biology., U.S. National Library of Medicine, Sept. 1995, www.ncbi.nlm.nih.gov/pubmed/8531199.

Strobel, C, et al. “Calcium Signalling in Medial Intercalated Cell Dendrites and Spines.” The Journal of Physiology., U.S. National Library of Medicine, 15 Aug. 2017, www.ncbi.nlm.nih.gov/pubmed/28594440.

These are some resources that I will be utilizing as I begin to edit this paper. Open to any other suggestions as well. Thanks! — Preceding unsigned comment added by Jarett.anderson (talk • contribs) 20:31, October 13, 2017 (UTC)

Those refs are not correct. The "U.S. National Library of Medicine" publishes Pubmed, the index. Please provide correct citations. There is a tool in the menu bar above the edit window (what you see, when you click "edit") - the right you see "cite". Please refer to the training material to see how to use it. The last citation should look like this: Strobel, C; Sullivan, RKP; Stratton, P; Sah, P (15 August 2017). "Calcium signalling in medial intercalated cell dendrites and spines". The Journal of physiology. 595 (16): 5653–5669. doi:10.1113/JP274261. PMID 28594440..

Also please use literature reviews or textbooks; please don't use what we call "primary sources", which are papers where scientists present their research. The last ref there -- PMID 28594440 -- is a primary source, that you should not use.

And please don't use refs older than 5 years or so. There is no reason to use the ref from 1995 that you list above. Thanks! Jytdog (talk) 19:34, 14 October 2017 (UTC)

• Unfortunately, I have decided to completely revert the addition. It was poorly written, poorly formatted, and poorly sourced, and it was absolutely full of factual errors. Normally, I would prefer to fix some things myself, and tag those that I did not fix, but there were simply too many problems here for me to do that. It is generally a bad idea to dump a large amount of text into a Wikipedia article in a single edit. If the material is to be added back, please do so as a series of small edits that can be evaluated one-by-one by other editors. --Tryptofish (talk) 22:52, 12 December 2017 (UTC)

Error in placement of S4 segment label in figure

In the first figure in the sidebar I believe there is an error in the placement of the "S4" label, it has been placed next to the S5 segment. Alimanfoo (talk) 12:47, 26 January 2018 (UTC)

Yes, you are right. I hope that the caption explaining the + charges clears that up, but maybe the figure should be revised. --Tryptofish (talk) 16:28, 26 January 2018 (UTC)