Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols.
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The effects of NO-related activity and cellular thiol redox state on basal L-type calcium current, ICa,L, in ferret right ventricular myocytes were studied using the patch clamp technique. SIN-1, which generates both NO. and O2-, either inhibited or stimulated ICa,L. In the presence of superoxide dismutase only inhibition was seen. 8-Br-cGMP also inhibited ICa,L, suggesting that the NO inhibition is cGMP-dependent. On the other hand, S-nitrosothiols (RSNOs), which donate NO+, stimulated ICa,L. RSNO effects were not dependent upon cell permeability, modulation of SR Ca2+ release, activation of kinases, inhibition of phosphatases, or alterations in cGMP levels. Similar activation of ICa,L by thiol oxidants, and reversal by thiol reductants, identifies an allosteric thiol-containing "redox switch" on the L-type calcium channel subunit complex by which NO/O2- and NO+ transfer can exert effects opposite to those produced by NO. In sum, our results suggest that: (a) both indirect (cGMP-dependent) and direct (S-nitrosylation/oxidation) regulation of ventricular ICa,L, and (b) sarcolemma thiol redox state may be an important determinant of ICa,L activity.
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Protein S-nitrosylation: Purview and parameters
Hess, D. T., Matsumoto, A., Kim, S.-O., Marshall, H. E., & Stamler, J. S. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1569 · Cited by 2,153 · see citing works
Self-citationPhysiology of Nitric Oxide in Skeletal Muscle
Stamler, J. S., & Meissner, G. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.209 · Cited by 1,080 · see citing works
Self-citationNitric oxide synthase in cardiac sarcoplasmic reticulum
Xu, K. Y., Huso, D. L., Dawson, T. M., Bredt, D. S., & Becker, L. C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.2.657 · Cited by 480 · see citing works
Stowe, D. F., & Camara, A. K. S. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2331 · Cited by 471 · see citing works
Allopurinol Improves Myocardial Efficiency in Patients With Idiopathic Dilated Cardiomyopathy
Cappola, T. P., Kass, D. A., Nelson, G. S., Berger, R. D., Rosas, G. O., Kobeissi, Z. A., Marbán, E., & Hare, J. M. (2001) · Circulation · doi:10.1161/hc4501.098928 · Cited by 436 · see citing works
Kanai, A. J., Pearce, L. L., Clemens, P. R., Birder, L. A., VanBibber, M. M., Choi, S.-Y., de Groat, W. C., & Peterson, J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.241380298 · Cited by 341 · see citing works
Cabungcal, J.-H., Steullet, P., Kraftsik, R., Cuenod, M., & Do, K. Q. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.09.020 · Cited by 232 · see citing works
Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart
Umar, S., & van der Laarse, A. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0219-x · Cited by 182 · see citing works
Is nitric oxide overproduction the target of choice for the management of septic shock?
Feihl, F., Waeber, B., & Liaudet, L. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(01)00155-3 · Cited by 151 · see citing works
Kulak, A., Steullet, P., Cabungcal, J.-H., Werge, T., Ingason, A., Cuenod, M., & Do, K. Q. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4858 · Cited by 124 · see citing works
Melanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers
Levin, M. D., Lu, M. M., Petrenko, N. B., Hawkins, B. J., Gupta, T. H., Lang, D., Buckley, P. T., Jochems, J., Liu, F., Spurney, C. F., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci39109 · Cited by 92 · see citing works
REACTIVE OXYGEN SPECIES IN CARDIAC SIGNALLING: FROM MITOCHONDRIA TO PLASMA MEMBRANE ION CHANNELS
Hool, L. C. (2006) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2006.04341.x · Cited by 83 · see citing works
Hool, L. C., & Arthur, P. G. (2002) · Circulation Research · doi:10.1161/01.res.0000035528.00678.d5 · Cited by 71 · see citing works
Baldus, S., Müllerleile, K., Chumley, P., Steven, D., Rudolph, V., Lund, G. K., Staude, H.-J., Stork, A., Köster, R., Kähler, J., et al. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.07.010 · Cited by 63 · see citing works
Chung, H. S., Kim, G. E., Holewinski, R. J., Venkatraman, V., Zhu, G., Bedja, D., Kass, D. A., & Van Eyk, J. E. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1712623114 · Cited by 33 · see citing works
Impact of dietary nitrate on age-related diastolic dysfunction
Rammos, C., Hendgen-Cotta, U. B., Totzeck, M., Pohl, J., Lüdike, P., Flögel, U., Deenen, R., Köhrer, K., French, B. A., Gödecke, A., et al. (2016) · European Journal of Heart Failure · doi:10.1002/ejhf.535 · Cited by 31 · see citing works
- Authors
- Campbell, D. L., Stamler, J. S., & Strauss, H. C.
- Affiliations
- Duke Medical Center (US)
- ORCID
- Stamler, J S
- Venue
- The Journal of general physiology
- Publisher
- Rockefeller University Press
- Published
- 1996-10-01
- Volume
- 108
- Issue
- 4
- Pages
- 277-293
- ISSN
- 0022-1295 (ISSN-L)
- 1540-7748
- PMC
- PMC2229328
- OpenAlex
- W2143855170
- Cited by
- 441
- References
- 104
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 13 · 2013: 12 · 2012: 25
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of General Physiology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k08hl002582-01, 5p50hl054314-05)
- National Heart, Lung, and Blood Institute (HL02582, HL 19216, HL-54314)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- L-type calcium channels, nitric oxide, S-nitrosothiols, thiol redox state, ventricular myocytes, ferrets, SIN-1, superoxide, S-nitrosylation, allosteric regulation, redox switch
- MeSH terms
- Animals, Extracellular Space, Ferrets, Heart Ventricles, Male, Molsidomine, Myocardium, Nitric Oxide, Nitroso Compounds, Oxidation-Reduction, Sulfhydryl Compounds, Calcium Channels, Patch-Clamp Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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