Ion Channels

Ion Channels

  • Christof Winkler-Hermaden added an answer:
    Can anyone recommend an antibody for the mitochondrial NCX?
    Experiments with the NCX blocker CGP-37157 indicate that NCXmito could be of importance in my model. To characterize this further, I would need an NCX antibody that is good for western blotting and immunocytochemistry.
    Christof Winkler-Hermaden · Karl-Franzens-Universität Graz

    We just started to work with MAB1789 against NCX from Abnova. I will let you know, if it is working well .

  • Leslie Rietveld added an answer:
    Does anybody have some experience with Kv1.3 western blots especially which antibodies to use?
    I have been unsuccessful with the detection of Kv1.3 in transfected cells using western blot even though the indirect detection via an N-terminal tag worked in immunofluorescence. Can someone help with a protocol specific for Kv1.3 especially which antibody to use?
    Leslie Rietveld · StressMarq Biosciences Inc

    Hi Welbeck,

    We have an antibody that is specific for Kv1.3 (Cat. # SMC-387D) and has been tested for use in Western blot using rat brain lysates. We offer a trial program where you can try a sample size (12ug) free, and all you have to pay for is shipping to your destination. This offer is available through our distributors Biomol and Biotrend in Germany as well.

    Best of luck!

  • Olga Krizanova added an answer:
    What would be a good option to specifically block the IP3R2 activity?

    We are interested in blocking the calcium efflux from the ER in hepatocytes, and turns out that they express mainly the type 2 of the IP3R. 2 APB may not work because it has more affinity for the types 1 and 3. What would be a good option to block the IP3R2 in these cell?  

    Olga Krizanova · Slovak Academy of Sciences

    We are using siRNA from Dharmacon, efficiency for the IP3R2 is about 70%. Xestospongin C is also an option, although it is not a type specific and moreover, not 100% specific for the IP3 receptors.

  • Maximiliano Jose Nigro added an answer:
    Does anyone have a protocol for examining the basic firing properties of a neuron using whole-cell patch clamp techniques in pClamp?

    I am trying to examine the active and passive firing properties of neurons from brain slices in vitro and need to know which properties are most beneficial to examine and the best protocol for examining these using whole cell patch clamp techniques. Most of what I have been finding in the literature involves using intracellular recordings to obtain the properties or have conducted these analyses in vivo. 

    Maximiliano Jose Nigro · New York University

    Hi Eric,

    No, it would not be accurate. You have to analyse those properties with Clampfit offline, or if you know how to automate analysis with MatLab it might be possible to do it during the experiment. I never measured those parameter with a Cs-based solution because that would block most of the potassium currents. Moreover you cannot record the firing activity of a neurons with a Cs-based pipette solution.

    The adaptation is a phenomenon by which the firing of a cell slows down during a train of action potentials. So in some cases (like CA1 pyramidal cells or stellate cells of the entorhinal cortex) the firing frequency is higher at the beginning of a train of action potentials than at the end. There are different mechanisms that underly adaptation in different cell types. For example, slow activating potassium channels, like Kv7. Also Ca-activated K channels that underly the slow AHP. Also the inactivation of Na channels can have a role in the adaptation.

    Different cell types can express different firing patterns some are regula firing (i.e. the interspike interval does not change during a train of spikes) some are adapting (i.e. the interspike interval is bigger at the end of a train than at its onset.

    I think it is more accurate to study the temporal distribution of spikes in a train in traces that contain the same number of spikes. In that way you can reduce variance due to differences in input resistance between cells or treatments (control vs drug).

    Of course the details of each protocol will depend on the properties of the cell type you want to study.

  • Rym Benkhalifa added an answer:
    I measured the function of the CNG channel in oocytes and we used KCl in both bath and pipette solutions. Can I use NaCl instead of KCl?
    I have a basic question about the solution that I used in my patch clamp experiments. I did inside out to measure the function of Cyclic-nucleotide gated channel which is a non selective cation channel, I used symmetric KCl in both bath and pipette solution.
    Now I am trying to find the correct answer to why our lab uses KCl but not NaCl or other salts. I got varieties of answers, someone told me that because of mobility of KCl or someone told that I could use NaCl also but our lab uses this for long time. Therefore, if you have any idea about my question please share.
    Rym Benkhalifa · Institut Pasteur de Tunis
    measuring non selective cation channels is possible with KCl or NaCl but usually KCl is prefered to avoid the intervention of additional parameters in the interpretation of results ... another reason, most electrophysiologist prefer to work with KCl to be close to physiological conditions.
    good luck
  • Jorge Parodi added an answer:
    How do I get APD50 using clampfit 9.2?
    .
    Jorge Parodi · Temuco Catholic University
    Hmm I never used clampfit for signal analisys, you can used minianalisys software, for the kinetic observation or used a trick, yo can convert the abf file in ASCII and open in origin problam and used the curve fit analsiys of the origin for obtanied values of your curve
    I hope you can resolve the problem
  • Kalpita Karan added an answer:
    Is anyone working with electrophysiology data of glutamate transporters?
    I am looking for some inputs on pulsing protocols for glutamate induced anion currents in whole cell patch clamp.
    Kalpita Karan · Jawaharlal Nehru Centre for Advanced Scientific Research
    Hi,

    No I havenot done that. As in only hold at -80 and taking multiple sweeps.

    Also, if I see changes in conductivity in a global profile across various constructs with a blocker in place, is it still not meaningful.

    I am having some issues with my amplifier, so cant run experiments. But I already have leak subtraction enables while taking a trace. Also I take without the leak subtraction.

    I am trying to understand the rationale behind not changing a voltage from holding, is it just to control any external effect apart from glutamate if I was looking at transporter current?

    Your inputs are appreciated.
  • Gabriele Scheler added an answer:
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  • Md.Mahbubur Rahman asked a question:
    What is the specific channel in a plasma membrane for Magnesium efflux from a cell?
    TRPM7 and TRPM6 is the channel which regulates influx of magnesium and calcium in cell. I want to know which channel regulate efflux of Mg?
    Could you please let me know?
  • Dina Simkin added an answer:
    Upright scope interferes with fast perfusion - any advice?
    I'm having some issues with fast perfusion on an upright scope. We normally do slice work so there hasn't been too much need for a picospritzer and fast perfusion until now. The objective seems to actually interfere with the flow (im guessing) so if I don't have the perfect bath level I sometimes don't get washing out of my glutamate puff from the picospritzer resulting in a persistent NMDA current (HEK cells on coverslips). So the peak and area of currents vary widely. Any recommendations for perfusion chambers or other solutions for this? I'm using a luigs & neimen stage (which I guess I can work around by using an adapter), homemade perfusion system (as you can see from attached pic) with vacuum suction or peristaltic pump suction.
    Dina Simkin · Northwestern University
    In the end what worked is moving the output to a 90 degree angle from the input and pico spritzer...now I get full perfusion after the puff and beautiful currents. Go figure.
  • Miroslav N Nenov added an answer:
    How we can differentiate capacitative current and ionic current in whole cell patch clamp recording?
    If we measure HEK293T cells transfected with sodium channels then is it possible to differentiate ionic current and capacitive current in measurement? Also, is it possible to quantify them separately?
    Miroslav N Nenov · University of Texas Medical Branch at Galveston
    Hi! Try to use TTX in addition to the answers listed above.
    Run your protocol for sodium current measurement then introduce TTX to the bath solution and repeat protocol again. Substract one trace from the other and you will get a trace without capacitive current but with sodium current in it.
    Best,
    Miroslav
  • Md. Shahidul Islam asked a question:
    Are any of you coming to the Calcium Signaling conference in Stockholm?
    "Calcium signaling: from basic to bedside" will be in the Scandic Victoria Tower Hotel, 3-5 July, 2014. See the details in www.calcium2014.com
  • Deepak Subramanian added an answer:
    How do you prevent spreading depression in High K+ model?
    I am currently using a high K+ model (8.5 mM K+ with 1mM CaCl2 and 1.3mM MgSO4) for inducing seizures in acute rat hippocampal slices (4-8wks old). Recently, we see a lot of spreading depression's (SDs) in our slices which makes it almost impossible to study any drug effects. Most of our slices start to show SDs within a few "ictal-like bursts" and then occur regularly after every ictal burst or once every 2-3 bursts. We also find the incidence of SDs to increase whenever the recorded potential (field) is of higher amplitude, usually stable until they exceed ~4-5mV.

    The slices are maintained at 34-35 C in an interface chamber (flowing) with a flow rate of 1.5ml/min and bubbled at a high rate. Potentials are recorded with a ~1mOhm glass electrode filled with high K+ acsf.

    Reducing temperature to 34 C and increasing flow rates doesn't seem to help much. Is there any other way to reduce SDs?
    Deepak Subramanian · Christian Medical College Vellore
    @Morten Jenson: Thank you very much for your suggestions! As you have mentioned, SD precisely occurs during early Ictal -Clonic phase, especially in slices which produce high amplitude activity. We have infact tried lowering the temperature down to 34C, which seems to do the trick sometimes but in some slices we also end up with more interictal-like bursts. We make 450uM slices and we oxygenate quite heavily.
    I will try reducing the KCl to 7.5mM and increasing CaCl2 to 1.2. Thank you!

    @Rubem Guedes: Thank you for you suggestion. I will try increasing calcium levels.
  • Tenzin Ngodup added an answer:
    Are there any proteins which are responsible for synaptic plasticity?
    Are there any proteins which can trigger synaptic plasticity or modulate synaptic plasticity?
    Tenzin Ngodup · University at Buffalo, The State University of New York
    Synaptic plasticity means changes in synaptic strength over time. There are numerous presynaptic and postsynaptic factors that could change synaptic strength. On the presynaptic side, changes in proteins regulating neurotransmitter release could change probability of release which will changes synaptic plasticity. And on the postsynaptic side, amount of receptors and state (desensitization or saturation) will also change synaptic plasticity.
  • Thuany Ribeiro Silva added an answer:
    Could anyone recommend to me articles about the electrophysiology of marine algae?
    For example, I'm looking for articles which talk about the action potential or ion channels present in seaweed Ulva lactuca Linnaeus, or path-clamp techniques performed in seaweed.
    Thuany Ribeiro Silva · Federal University of Rio de Janeiro
    Thank you so much!
  • Jonathan T Ting added an answer:
    Can channelrhodopsin and halorhodopsin be expressed in the same neurons?
    I am trying to find a way to induce the excitation and inhibition on the same set of neurons that are relevant to a particular behavior in rodents. Can you express both of these opsins in the same cell and activate them alternately and simultaneously?
    Jonathan T Ting · Allen Institute for Brain Science
    You can express both in the same cell using Cre/loxP. You would ideally have both genes in a single double-floxed cassette e.g. viral vector with DIO design. You could then inject that virus into the brain of a mouse or rat with cell type specific cre recombinase expression. That would be the obvious way. If you have ChR2 and NpHR on separate expression vectors, e.g. two independent DIO viral vectors, this could in principle cause some issues with undesirable recombination events when virus is co-injected into a Cre mouse, but I have not tried this.
  • Jordi Heijman added an answer:
    Can anybody tell me what the 9 states of the single sodium ion channel model actually represent?
    I'm working on the sodium ion channel model which has 9 coupled state. The model is the single sodium ion channel model of Dr. Vandenberg, C.A. and Dr.F. Bezanilla. See "A sodium channel gating model based on single channel, macroscopic ionic, and gating currents in the squid giant axon," Biophys. J. Biophysical Society, Volume 60 December (1991) 1511-1533 . I'm not able to understand the physical significance of these states. What do these states represent? The sodium channel consists of 4 repetitive segments of alpha protein each having 6 domains (consisting of S1-S6). So what does this mathematical model suggest? (the model is roughly given in the attachment)

    Where,

    1. u is a fitting parameter of experimental work, u=constant.

    2. a_i,b_i are the transition probabilities, which are voltage (V) dependent. The functional forms of a_i and b_i are written at the bottom right corner.

    3. there are 9 states (p0,p1,...p8) which are coupled. P is the probability at time t.

    4. a_i0, b_i0 are the transition probabilities when there is no Voltage applied.

    5. Do not look at the functional forms and associated parameters, they are constants for V= constant.

    p0--->p4= resting to activated state
    p5= channel open state,
    p6,p7,p8= inactive states.

    How do these states correspond to the actual structure of single voltage gated sodium ion channels?
    Jordi Heijman · University Hospital Essen
    Great addition, William!

    One advantage of (some) Markov models is that they allow simulation of state-specific drug binding, something that is not always (easily) achieved with traditional Hodgkin-Huxley formulations. A nice example for the Na+-channel, comparing open and inactivated state block can be found in Clancy et al. Am. J. Physiol. Heart. Circ. Physiol. 2007 (http://www.ncbi.nlm.nih.gov/pubmed/16997895)
  • Tooraj Mirshahi added an answer:
    Which is much better for expression of alpha 2 beta 4 neuronal receptors in ooytes, injecting mRNA or cDNA?
    We want to perform outside out patching in oocytes. Therfore, we injected mRNA in 1:10 (alpha:beta) ratio. Patching was done after 3 days of injection and we applied 50 micromolar of Ach solution, but we failed to get any result. From literature we learned that it is also possible to inject cDNA. Is injecting cDNA is better over mRNA for getting current?
    Tooraj Mirshahi · Geisinger Medical Center
    Injecting mRNA is much easier and typically gives more consistent oocyte to oocyte expression. There are some labs that routinely inject cDNA and get it to work, but if look through the literature most labs still use RNA.
    A few important considerations:
    First, if you inject cDNA make sure you inject directly into the nucleus and keep the volume down (5-10 nL), you can practice nuclear injections using dye (diluted DNA loading dye is a good choice). After you inject the dye, pop the oocytes and see if you hit the target, the nucleus will be right under the dark pole and should be full of blue dye.
    Second consideration in the vector you use. A CMV promoter works well for cDNA injected expression.
    Finally, have you tested your oocytes for whole cell currents (two-electrode voltage clamp)? It is a lot easier to determine your expression using TEVC than doing outside-out patches. If you do not have large enough currents in whole cell, you will have a hard time getting currents in outside-out patches.
    Good luck.
  • Abbas Burhan Qadir Salihi added an answer:
    Does anyone know how many patch clampers are in the world, and how many patch clamp rigs?
    Patch clamp.
    Abbas Burhan Qadir Salihi · Salahaddin University - Hawler
    Nice question.. I think alot.....
  • David Baez-Nieto added an answer:
    Beyond the obvious size and charge restrictions, how does ion channel selectivity work?
    While I can understand how a protein channel in the membrane can select against ions that are too large to pass through them, or utilize charged amino acids to prevent an influx of the wrong charge, I'm having a tough time understanding how it works specificity past that point.
    In essence, if you have an ion channel which allows a larger cation in or out of a cell, what prevents it from letting smaller cations in or out? Or do those smaller particles travel more freely and just have to be balanced by pumps within the membrane, etc.?
    David Baez-Nieto · Universidad de Valparaíso (Chile)
    I really like the previous answer, and I think is the best way to understand the permeation mechanism in a didactic way. In addition I would like to say something about the ion dehydration during the permeation process. K+ ions are usually coordinated by 1 shell of 6-8 water molecules, on the other hand Ca+2 is likely to have a shell with two water layers... so in terms of dehydration energy is quite expensive to permeate Ca+2 than K+ from a energetic point of view (a very simple one). Now, if you want to understand the ion radii in permeation Cs+ permeation in K+ channels is an excellent example. Most will say that Cs+ ions blocks the K+ current, but actually what occurs is that Cs+ ion permeates through K+ channels, but a very slow rate. So what is happening is that different ions have different residence time inside the selectivity filter, in this case K+ ions are permeated at 10E6 ions per second instead Cs+ is permeated 10E0 per second for example, the same is true for Ba+2 and K+ channels. You should read http://www.ncbi.nlm.nih.gov/pubmed/10469727 for the last example.
  • James P Dilger added an answer:
    Difficulty in outside-out patching
    I tried doing outside-out patch in HEK cells containing nAchr. When I apply Ach solution, it's very rare that I get a current. Can someone suggest the way it should be performed or a reason for why I am not getting a current?
    James P Dilger · Stony Brook University
    Hello Abhilasha and Jana, Sorry for not getting back to you sooner.

    It sounds like your methods are fine. Focusing on cells with higher fluorescence should be beneficial. One day after transfection sounds a bit too early but 2-3 days should be fine. I used to use calcium phosphate and had good results. At some point, we switched to Fugene 6 because it is a little simpler to use (the size of the precipitate is critical with Ca phosphate) and may be gentler on the cells. It really didn't make any noticeable change in the transfection efficiency.

    If you haven't done so recently, you could check the concentration of your cDNA vials. Too much or too little of a particular subunit may reduce efficiency. Also, endotoxin contamination in the cDNA might cause problems. We routinely pay a little extra to have Genewiz provide us with endotoxin-free cDNA.

    Happy to (try to) help,
    Jim
  • Krishnendu Pal added an answer:
    Time dependent solution of the master equation of a complex system,question follows:
    Is it possible to solve a time dependent solution of a classical master equation using the generating function method, where the transition probabilities are state dependent?
    I want to solve the time dependent solution for the 9 coupled state of single sodium ion channel model of Dr. Vandenberg, C.A. and Dr.F. Bezanilla. See "A sodium channel gating model based on single channel, macroscopic ionic, and gating currents in the squid giant axon.,Biophys. J. Biophysical Society,Volume 60 December (1991) 1511-1533
    Krishnendu Pal · S.N. Bose National Centre for Basic Sciences
    well sir, if you get spare times from your busy schedule someday, i'm giving you the details...I really need a suggestion. Looking forward to your kind attention.
    1. that is not u^V, that is u**2 . u is a fitting parameter of experimental work, u=constant.
    2. a_i,b_i are the transition probabilities, which are voltage(V) dependent. The functional forms of a_i and b_i are written at the bottom right corner.
    3. there are 9 states(p0,p1,...p8). which are coupled. P is the probability at time t.
    yes differentiation with respect to t (time).
    4. a_i0, b_i0 are the transition probabilities when there is no Voltage applied.
    5. Do not look at the functional forms and associated parameters, they are constants for V= constant. I want the constant voltage solution, which means a_i, b_i these transition probabilities are constant.
    6. I want the time dependent expressions of each probabilities, i.e. P(n,t). As it is a case of 9 coupled differential equation we cannot use general techniques for solving. We need general master equation.
    7. the general master equation looks like the following when the model reduces to a linear looking model:

    dP(n,t)/dt = k_1^{(n-1)} P(n-1,t) + k_{-1}^{(n+1)} P(n+1,t) - [k_1^(n)+k_{-1}^(n)]P(n,t)

    where,
    k_1 =forward transition rates,i.e. a_i, the (n+1)or(n-1)or n above k_1 are the state indexes.
    k_{-1}= backward transition rates,i.e, b_i, the (n+1)or(n-1)or n above k_1 are the state indexes.
    we need to solve P(n,t). One way of solving is using generating function method(paper attached herewith, D.A. Mcquarrie. page 419
    which I'm not being able to solve analytically bcoz the transition probabilities are state dependent.
  • Athena Akrami added an answer:
    DREADD vs. optogenetics
    I am thinking of employing both these techniques in my lab and was wondering if people would like to share their thoughts/experience.

    From a behavioural point of view I suppose that a major advantage of optogenetics is that you have greater temporal control over stimulation: once a dose of CNO is administered to an animal expressing DREADD there is presumably a time-to-onset and later a decline in receptor occupation and effect, whereas with ChR2/NpHR simulation is phase-locked to light stimulation.

    By contrast, I would imagine that light scattering (optic fibre in brain)/failure of light to penetrate tissue sufficiently (stimulation of peripheral nerves in skin) is a drawback of optogenetic stimulation compared to oral administration of CNO, which has known efficacy at different DREADDs.

    Any thoughts/comments welcomed!
    Athena Akrami · Princeton University
    Dear Dimitri, Thanks a lot for the references.
  • Henrique P. von Gersdorff added an answer:
    AHP (after hyperpolarization) time to peak is determined by which ion channel?
    Which ion channel is responsible for AHP time to peak?
    Henrique P. von Gersdorff · Oregon Health and Science University
    After a high frequency train of stimuli the AHP may have a significant contribution from the activation of Na/K-ATPase pump. In the calyx of Held this is the case and also in some pyramidal neurons in the hippocampus (See Kim et al., Nat. Neurosci. 2007).
  • Christian Rosker added an answer:
    If one uses caffeine to deplete calcium storage in smooth muscle cells, will increasing [Ca2+] in saline elicit greater contractions than baseline?
    I am currently in a experimental physiology class and my final research project is on this very question . My thinking behind the question is that depleting internal calcium storage will cause activation of slow voltage gated calcium channels that will allow an influx of calcium from the saline solution. Since calcium will be moving with its gradient, it will flow into the smooth muscle cell and elicit a stronger and quicker contraction. The concentrations being tested are 0mM (control), 9mM, 12mM, and 15mM. The smooth muscle samples come from an earthworm's crop and gizzard. Earthworm saline without any manipulation has [3mM] of calcium. So far, I've received results where the largest concentrations have an initial contraction, then a quick decline to flatline. Once I introduce normal saline to the same sample, the contractions are brought back to baseline, so the sample isn't dead. My control also showed strong, lasting contractions. Could anyone give me some insight to what is going on?
    Christian Rosker · Medical University of Graz
    Appart from theory I guess it depends on timing too, the longer you keep your cells in calcium free alive the quicker/larger the response might be as soon as you provide enough external calcium again. The players involved are various ion channels and pumps what makes it sort of difficult to attribute the final contraction to your caffeine treatment. If you want to get into details here replace your calcium in the external solution by some cation that is not contained in the internal stores... Good luck!
  • Franco Lombino added an answer:
    Single channel recording
    Are you really recording from a single molecule?
    Franco Lombino · Albert Einstein College of Medicine
    All your contributions are really appreciated. Thanks guys.
  • Kristopher Sheets added an answer:
    Image analysis to count and measure the diameters and fluorescence intensity of immunofluorescent neuronal somata?
    I have fluorescent images with labeled neurons and I need to count, analyze and sort them by size and fluorescence intensity. I have plenty of these images so I don't want to do this manually with Photoshop or ImageJ. I also have to do similar measurements with immunolabeled punctate labels that stain receptor plaques on the surface of the cells.

    Does anyone knows an automated, and ideally free, piece of software that does that? Perhaps ImageJ and/or Fiji has some script that I'm not aware of?
    Kristopher Sheets · University of California, Los Angeles
    Here is a quick guide to doing this in Fiji/ImageJ. This assumes a 2D image of a single fluorescent label. You will need the hysteresis thresholding plugin written by Thomas Boudier. Download at http://imagejdocu.tudor.lu/doku.php?id=plugin:segmentation:hysteresis_thresholding:start

    In Fiji or ImageJ, open the macro editor under the menu Plugins>New>Macro then paste the following and run it for an example. Change step 2 to open your image, or omit it to run on an already open image. Adjust the lower and upper threshold values for the hysteresis plugin to get optimal results.

    // 1. set up the measurements
    run("Set Measurements...", "area feret's integrated redirect=None decimal=9");
    run("Colors...", "foreground=white background=black selection=red");


    // 2. open your image
    // The invert step is a custom step to mimic fluorescent image.
    // It only applies to the CellColony image
    run("Cell Colony (31K)");
    imp=getImageID();
    title=getTitle();
    run("Invert");

    // 3. subtract background if illumination is uneven
    run("Subtract Background...", "rolling=128 sliding");

    // 4. run hysteresis thresholding
    // this method determines the lower threshold with the Huang method
    // and the upper threshold with the Yen method. Change methods as necessary
    // to get a better fit. Optionally, hard value limits can be used
    setAutoThreshold("Huang dark");
    getThreshold(lowerHuang,upperHuang);
    setAutoThreshold("Yen dark");
    getThreshold(lowerYen,upperYen);
    resetThreshold
    run("hysteresis ", "high="+lowerYen+" low="+lowerHuang);

    // 5. watershed the hysteresis image
    selectWindow("Hysteresis");
    run("Watershed");

    // 6. analyze particles to get results
    run("Analyze Particles...", "size=0-Infinity circularity=0.00-1.00 show=Nothing display add in_situ");


    // cleanup actions
    selectWindow("Trinarisation");
    rename(title+"_Trinarisation");
    selectWindow("Hysteresis");
    rename(title+"_Hysteresis");
    selectImage(imp);
    roiManager("Show All without labels");
  • Ralf Kettenhofen added an answer:
    Why is hERG activity evaluated in relation to kinase inhibitors?
    hERG is related to cardiac rhythm and is evaluated mainly in relation to kinase inhibition. Why is this?
    Ralf Kettenhofen · Axiogenesis AG
    Arvind, could you specific the context for your question?
    Regarding the pharmaceutical industries effords to make safe drugs, hERG inhibition was considered to be a predictive biomarker for life threatening Torsade-de-Pointes left ventricular arrhythmias since the hERG channel is the major repolarising component during the action potental of cardiomyocytes.
    In the context of anti-cancer drug developement, protein kinase inhibitors are still in the focus ot the pharma industry because they can be used to to arrest or kill cancer cells. Some of the older and less specific inhibitors have severe cardiac side effects due to cardiac cytotoxicity as mentioned by Helena. This has nothing to do with the hERG channel block (activity). But it was found that potassium channels (especially the hERG channel) are upregulated in cancer cells. Unfortunately, I am not too much into the matter of oncology but maybe there exist comparisons in the potency of hERG blockers and protein kinase inhibitors to arrest or kill cancer cells.

    Here you can find a link to an abstract of an article concerning the rule of hERG the channel in cancer cells:
    http://www.ncbi.nlm.nih.gov/pubmed/23970866

    Best regards,

    Ralf

About Ion Channels

Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.

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