Effects of Perfluorooctane Sulfonate on Action Potentials and Currents in Cultured Rat Cerebellar Purkinje Cells
Abstract
Recently, PFOS was reported to be ubiquitously detected in the environment, as well as in human serum, raising concerns regarding its health risks. We investigated the effects of PFOS on action potentials and currents in cultured rat cerebellar Purkinje cells using whole-cell patch-clamp recording. In current-clamp experiments, PFOS significantly decreased the action potential frequency during current injection, the maximum rate of fall and the threshold of action potential, and negatively shifted the resting membrane potential at doses over 30microM. In voltage-clamp experiments, PFOS shifted the half-activation and inactivation voltages of I(Ca), I(Na), and I(K) toward hyperpolarization at 30microM. I(HCN1) expressed in Xenopus oocytes was similarly affected. Incorporation of PFOS into the cell membrane probably increased the surface negative charge density, thereby reducing the transmembrane potential gradient and resulting in hyperpolarizing shifts of both the activation and inactivation of ionic channels. These findings indicate that PFOS may exhibit neurotoxicity.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Several Ca2+ dependent signaling molecules, including CaMKII, CREB, and calcineurin, have been shown to be sensitive to PFAS exposure.
“Several Ca2+ dependent signaling molecules, including Ca2+/calmodulin-dependent protein kinase II (CaMKII), cAMP-response element binding protein (CREB), and calcineurin (CaN) have also been shown to be sensitive to PFAS exposure”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Harada et al., 2006
PFOS can impact gating properties of sodium and potassium channels, but only at high concentrations above 30 μM, and nonspecific membrane impacts cannot be ruled out.
“There are some data showing that PFOS can impact gating properties of sodium and potassium channels, ions critical for forming electrical impulses (i.e., action potentials). However, these studies only report significant effects at high concentrations, above 30 µM, and cannot rule out nonspecific membrane impacts (Harada et al., 2006).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Harada et al., 2006
Cites
The action of calcium on the electrical properties of squid axons
FRANKENHAEUSER, B., & Hodgkin, A. L. (1957) · The Journal of Physiology · doi:10.1113/jphysiol.1957.sp005808 · Cited by 1,839 · see citing works
Charges and Potentials at the Nerve Surface
Hille, B. (1968) · The Journal of General Physiology · doi:10.1085/jgp.51.2.221 · Cited by 563 · see citing works
Perfluorinated compounds in aquatic organisms at various trophic levels in a Great Lakes food chain
Kannan, K., Tao, L., Sinclair, E., Pastva, S. D., Jude, D. J., & Giesy, J. P. (2005) · Archives of Environmental Contamination and Toxicology · doi:10.1007/s00244-004-0133-x · Cited by 530 · see citing works
Perfluorooctanoate and Perfluorooctane Sulfonate Concentrations in Surface Water in Japan
Saito, N., Harada, K. H., Inoue, K., Sasaki, K., Yoshinaga, T., & Koizumi, A. (2004) · Journal of Occupational Health · doi:10.1539/joh.46.49 · Cited by 302 · see citing works
Harada, K. H., Inoue, K., Morikawa, A., Yoshinaga, T., Saito, N., & Koizumi, A. (2005) · Environmental Research · doi:10.1016/j.envres.2004.12.003 · Cited by 286 · see citing works
Concentrations of perfluorinated acids in livers of birds from Japan and Korea
Kannan, K., Choi, J., Iseki, N., Senthilkumar, K., Kim, D. H., Masunaga, S., & Giesy, J. P. (2002) · Chemosphere · doi:10.1016/s0045-6535(02)00304-1 · Cited by 220 · see citing works
Ohmori, H., & Yoshii, M. (1977) · The Journal of Physiology · doi:10.1113/jphysiol.1977.sp011821 · Cited by 187 · see citing works
Harada, K. H., Saito, N., Inoue, K., Yoshinaga, T., Watanabe, T., Sasaki, S., Kamiyama, S., & Koizumi, A. (2004) · Journal of Occupational Health · doi:10.1539/joh.46.141 · Cited by 186 · see citing works
A Molecular Structural Basis for the Excitation Properties of Axons
Goldman, D. E. (1964) · Biophysical Journal · doi:10.1016/s0006-3495(64)86776-x · Cited by 165 · see citing works
Perfluorinated chemicals in selected residents of the American continent
Calafat, A. M., Needham, L. L., Kuklenyik, Z., Reidy, J. A., Tully, J. S., Aguilar-Villalobos, M., & Naeher, L. P. (2005) · Chemosphere · doi:10.1016/j.chemosphere.2005.08.028 · Cited by 162 · see citing works
Mass Budget of Perfluorooctane Surfactants in Lake Ontario
Boulanger, B. O., Peck, A. M., Schnoor, J. L., & Hornbuckle, K. C. (2004) · Environmental Science & Technology · doi:10.1021/es049044o · Cited by 146 · see citing works
Cultivation of mouse cerebellar cells in serum free, hormonally defined media: Survival of neurons
Fischer, G. (1982) · Neuroscience Letters · doi:10.1016/0304-3940(82)90079-9 · Cited by 122 · see citing works
Effects of PFOS and PFOA on L-type Ca2+ currents in guinea-pig ventricular myocytes
Harada, K. H., Xu, F., Ono, K., Iijima, T., & Koizumi, A. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.163 · Cited by 117 · see citing works
Determinants of activation kinetics in mammalian hyperpolarization‐activated cation channels
Ishii, T. M., Takano, M., & Ohmori, H. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0093k.x · Cited by 94 · see citing works
Morikawa, A., Kamei, N., Harada, K. H., Inoue, K., Yoshinaga, T., Saito, N., & Koizumi, A. (2005) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2005.03.007 · Cited by 81 · see citing works
Nakayama, S. F., Harada, K. H., Inoue, K., Sasaki, K., Benjamin, S., Saito, N., & Koizumi, A. (2005) · PubMed · Cited by 75 · see citing works
Weber, A., & Schachner, M. (1984) · Brain Research · doi:10.1016/0006-8993(84)91404-5 · Cited by 74 · see citing works
Harada, K., Nakanishi, S., Sasaki, K., Furuyama, K., Nakayama, S., Saito, N., Yamakawa, K., & Koizumi, A. (2006) · Bulletin of Environmental Contamination and Toxicology · doi:10.1007/s00128-006-0922-1 · Cited by 71 · see citing works
Self-citationVoltage-gated and synaptic currents in rat Purkinje cells in dissociated cell cultures.
Hirano, T., & Ohmori, H. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.6.1945 · Cited by 48 · see citing works
Fakler, B., Herlitze, S., Amthor, B., Zenner, H., & Ruppersberg, J. P. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33991-1 · Cited by 44 · see citing works
Effects of perfluorinated amphiphiles on backward swimming in Paramecium caudatum
Matsubara, E., Harada, K. H., Inoue, K., & Koizumi, A. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.11.048 · Cited by 33 · see citing works
A novel Ca2+ indicator protein using FRET and calpain-sensitive linker
Takatsuka, K., Ishii, T. M., & Ohmori, H. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.08.089 · Cited by 13 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Toxicology of perfluorinated compounds
Stahl, T., Mattern, D., & Brunn, H. (2011) · Environmental Sciences Europe · doi:10.1186/2190-4715-23-38 · Cited by 432 · see citing works
Developmental Neurotoxicity of Perfluorinated Chemicals Modeled <i>in Vitro</i>
Slotkin, T. A., MacKillop, E. A., Melnick, R. L., Thayer, K. A., & Seidler, F. J. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.11253 · Cited by 225 · see citing works
Starnes, H. M., Rock, K. D., Jackson, T. W., & Belcher, S. M. (2022) · Frontiers in Toxicology · doi:10.3389/ftox.2022.881584 · Cited by 166 · see citing works
Brown-Leung, J. M., & Cannon, J. R. (2022) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.2c00072 · Cited by 164 · see citing works
Jing, P., Rodgers, P. J., & Amemiya, S. (2009) · Journal of the American Chemical Society · doi:10.1021/ja807961s · Cited by 158 · see citing works
Jin, Y., Saito, N., Harada, K. H., Inoue, K., & Koizumi, A. (2007) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.212.63 · Cited by 129 · see citing works
Harada, K. H., Hashida, S., Kaneko, T., Takenaka, K., Minata, M., Inoue, K., Saito, N., & Koizumi, A. (2007) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2007.04.003 · Cited by 121 · see citing works
Binding of PFOS to Serum Albumin and DNA: Insight into the Molecular Toxicity of Perfluorochemicals
Zhang, X., Chen, L., Fei, X.-C., Ma, Y.-S., & Gao, H.-W. (2009) · BMC Molecular Biology · doi:10.1186/1471-2199-10-16 · Cited by 119 · see citing works
Li, Z., Dong, G., Jin, Y., & He, Q. (2008) · Archives of Toxicology · doi:10.1007/s00204-008-0361-3 · Cited by 119 · see citing works
Lau, C. S. (2012) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-7643-8340-4_3 · Cited by 103 · see citing works
Tukker, A. M., Bouwman, L. M. S., van Kleef, R. G. D. M., Hendriks, H. S., Legler, J., & Westerink, R. H. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-62152-2 · Cited by 90 · see citing works
Liu, X., Jin, Y., Liu, W., Wang, F., & Hao, S. (2011) · Toxicology in Vitro · doi:10.1016/j.tiv.2011.04.016 · Cited by 91 · see citing works
Fujii, Y., Niisoe, T., Harada, K. H., Üemoto, S., Ogura, Y., Takenaka, K., & Koizumi, A. (2014) · Journal of Occupational Health · doi:10.1539/joh.14-0136-oa · Cited by 89 · see citing works
Fluorine Mass Balance Analysis of Effluent and Sludge from Nordic Countries
Aro, R., Eriksson, U., Kärrman, A., Chen, F., Wang, T., & Yeung, L. W. Y. (2021) · ACS ES&T Water · doi:10.1021/acsestwater.1c00168 · Cited by 83 · see citing works
Perfluoroalkyl Chemicals in Neurological Health and Disease: Human Concerns and Animal Models
Piekarski, D., Diaz, K., & McNerney, M. (2020) · NeuroToxicology · doi:10.1016/j.neuro.2020.01.001 · Cited by 76 · see citing works
Elevated levels of perfluoroalkyl substances in estuarine sediments of Charleston, SC
White, N. D., Balthis, L., Kannan, K., Silva, A. O. D., Wu, Q., French, K., Daugomah, J. W., Spencer, C., & Fair, P. A. (2015) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2015.03.078 · Cited by 75 · see citing works
Jeong, T., Min-Su, Y., Jeon, J., & Kim, S. D. (2016) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2016.06.249 · Cited by 74 · see citing works
Neurotoxic effects of perfluoroalkyl acids: Neurobehavioral deficit and its molecular mechanism
Wang, Y., Wang, L., Chang, W., Zhang, Y., Zhang, Y., & Liu, W. (2019) · Toxicology Letters · doi:10.1016/j.toxlet.2019.01.012 · Cited by 60 · see citing works
PFAS: exploration of neurotoxicity and environmental impact
Nannaware, M., Mayilswamy, N., & Kandasubramanian, B. (2024) · Environmental Science and Pollution Research · doi:10.1007/s11356-024-32082-x · Cited by 66 · see citing works
Irie, T., Matsuzaki, Y., Sekino, Y., & Hirai, H. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.264309 · Cited by 59 · see citing works
Liu, X., Liu, W., Jin, Y., Yu, W., Wang, F., & Liu, L. (2009) · Archives of Toxicology · doi:10.1007/s00204-009-0467-2 · Cited by 57 · see citing works
Power, M. C., Webster, T. F., Baccarelli, A., & Weisskopf, M. G. (2012) · Neuroepidemiology · doi:10.1159/000342310 · Cited by 55 · see citing works
Liu, X., Liu, W., Jin, Y., Yu, W., Liu, L., & Yu, H. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0517-9 · Cited by 48 · see citing works
Chen, X., Nie, X., Mao, J., Zhang, Y., Yin, K., & Jiang, S. (2018) · NeuroToxicology · doi:10.1016/j.neuro.2018.03.003 · Cited by 48 · see citing works
Liao, C., Cui, L., Zhou, Q., Duan, S., & Jiang, G. (2008) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2008.11.013 · Cited by 47 · see citing works
Harada, K. H., & Koizumi, A. (2008) · Environmental Health and Preventive Medicine · doi:10.1007/s12199-008-0058-5 · Cited by 47 · see citing works
Perfluorododecanoic Acid Induces Cognitive Deficit in Adult Rats
Kawabata, K., Matsuzaki, H., Nukui, S., Okazaki, M., Sakai, A., Kawashima, Y., & Kudo, N. (2017) · Toxicological Sciences · doi:10.1093/toxsci/kfx058 · Cited by 37 · see citing works
Yang, J., Wang, C., Nie, X., Shi, S., Xiao, J., Ma, X., Dong, X., Zhang, Y., Han, J., Li, T., et al. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.05.019 · Cited by 34 · see citing works
López-Doval, S., Salgado, R., & Lafuente, A. (2016) · Chemosphere · doi:10.1016/j.chemosphere.2016.04.081 · Cited by 33 · see citing works
Perfluorooctane Sulfonate Induces Apoptosis in N9 Microglial Cell Line
Zhang, L., Li, Y., Zeng, H., Li, M., Wan, Y., Schluesener, H. J., Zhang, Z., & Xu, S. (2010) · International Journal of Toxicology · doi:10.1177/1091581810387832 · Cited by 28 · see citing works
Choi, S., Kim, J., Park, J., Lee, K., Kim, E., & Jeon, W. B. (2013) · Food and Chemical Toxicology · doi:10.1016/j.fct.2013.07.070 · Cited by 21 · see citing works
Effects of perfluorooctane sulfonate on tracheal ciliary beating frequency in mice
Matsubara, E., Nakahari, T., Yoshida, H., Kuroiwa, T., Harada, K. H., Inoue, K., & Koizumi, A. (2007) · Toxicology · doi:10.1016/j.tox.2007.04.016 · Cited by 21 · see citing works
Huang, Y., Chen, W., Gan, Y., Liu, X., Tian, Y., Zhang, J., & Li, F. R. (2024) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2024.135857 · Cited by 21 · see citing works
Vilchez, V., Turcios, L. M., Zaytseva, Y. Y., Stewart, R. L., Lee, E. Y., Maynard, E. C., Shah, M. B., Daily, M. F., Tzeng, C.-W. D., Davenport, D. L., et al. (2016) · The American Journal of Surgery · doi:10.1016/j.amjsurg.2015.12.019 · Cited by 20 · see citing works
Ortiz‐Sánchez, P. B., Roa-Espitia, A. L., Fierro, R., López-Torres, A. S., Jiménez‐Morales, I., Oseguera-López, I., Hernández-González, E. O., & González‐Márquez, H. (2022) · Reproductive Toxicology · doi:10.1016/j.reprotox.2022.03.013 · Cited by 19 · see citing works
Mailloux, R. J., Fu, A., Florian, M., Petrov, I., Chen, Q., Coughlan, M. C., Mahemuti, L., Yan, J., Caldwell, D., Patry, D., et al. (2015) · Toxicology · doi:10.1016/j.tox.2015.06.001 · Cited by 19 · see citing works
Lagostena, L., Rotondo, D., Gualandris, D., Calisi, A., Lorusso, C., Magnelli, V., & Dondero, F. (2024) · Journal of Xenobiotics · doi:10.3390/jox14040094 · Cited by 18 · see citing works
Mousavi, S. E., Yu, Q., & Shin, H. (2025) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2025.178972 · Cited by 13 · see citing works
Effects of perfluorooctane sulfonate (PFOS) on cognitive behavior and autophagy of male mice
Zhou, A.-J., Wang, L., Pi, X., Fan, C., Chen, W., Wang, Z., Rong, S., & Wang, T. (2023) · The Journal of Toxicological Sciences · doi:10.2131/jts.48.513 · Cited by 11 · see citing works
Kawamoto, K., Sato, I., Tsuda, S., Yoshida, M., Yaegashi, K., Saito, N., Liu, W., & Jin, Y. (2011) · The Journal of Toxicological Sciences · doi:10.2131/jts.36.55 · Cited by 9 · see citing works
Dendritic cell vaccines in metastasized malignant melanoma.
Erdmann, M., & Schuler‐Thurner, B. (2008) · PubMed · Cited by 9 · see citing works
Mousavi, S. E., Zarean, M., Yu, Q., Abbasi, S., & Kwong, R. W. M. (2025) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2025.181170 · Cited by 7 · see citing works
Park, Y., Suvorov, A., Symington, S., & Clark, J. M. (2022) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112804 · Cited by 5 · see citing works
Florian, M., Yan, J., Ulhaq, S., Coughlan, M. C., Mahemuti, L., Willmore, W. G., & Jin, X. (2013) · Toxicology · doi:10.1016/j.tox.2013.01.018 · Cited by 7 · see citing works
Roy, V. C., Bala, R., & Mehta, S. (2025) · Journal of Environmental Science and Health Part C · doi:10.1080/26896583.2025.2460884 · Cited by 6 · see citing works
PFOS disrupts key developmental pathways during hiPSC-derived cardiomyocyte differentiation in vitro
Davidsen, N., Ramhøj, L., Kugathas, I., Evrard, B., Darde, T., Chalmel, F., Svingen, T., & Rosenmai, A. K. (2022) · Toxicology in Vitro · doi:10.1016/j.tiv.2022.105475 · Cited by 6 · see citing works
Viberg, H., & Mariussen, E. (2015) · Molecular and integrative toxicology · doi:10.1007/978-3-319-15518-0_9 · Cited by 5 · see citing works
Neurochemical mechanisms of perfluoroalkyl substances (PFAS) neurotoxic action
Brown-Leung, J. M., & Cannon, J. R. (2023) · Advances in neurotoxicology · doi:10.1016/bs.ant.2023.08.002 · Cited by 5 · see citing works
Denslow, N. D., & Martyniuk, C. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-88462-4.00018-3 · Cited by 4 · see citing works
Fujii, Y., & Harada, K. H. (2025) · Chemosphere · doi:10.1016/j.chemosphere.2025.144409 · Cited by 2 · see citing works
Chemical speciation significantly shapes the neurotoxicity of perfluoroalkyl acids
Li, J., Ahmad, M., Chen, L., & Shi, J. (2026) · Environmental Pollution · doi:10.1016/j.envpol.2026.128499 · Cited by 1 · see citing works
Harada, K. H., & Okuda, H. (2023) · Environmental Science & Technology · doi:10.1021/acs.est.3c04278 · Cited by 1 · see citing works
Toxicología del sulfonato de perfluorooctano (PFOS) como modelo de compuesto orgánico fluorado
Pereiro, N., & Lafuente, A. (2012) · Redalyc (Universidad Autónoma del Estado de México)
Marinello, W. P., & Zylka, M. J. (2026) · Frontiers in Toxicology · doi:10.3389/ftox.2026.1814052
Kim, H. (2026) · Archives of Toxicology · doi:10.1007/s00204-026-04607-5
Organohalides and mitochondrial toxicity
Denslow, N. D., & Martyniuk, C. J. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45078-5.00031-2
- Authors
- Harada, K. H., Ishii, T. M., Takatsuka, K., Koizumi, A., & Ohmori, H.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Koizumi, Akio
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 351
- Issue
- 1
- Pages
- 240-245
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2091399681
- Cited by
- 58
- References
- 22
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (17-1910)
- Ministry of Education, Culture, Sports, Science and Technology (17023027-0133)
- Ministry of Health, Labour and Welfare (H15-Chemistry-004)
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- PFOS, Purkinje cells, cerebellum, action potential, ionic currents, HCN1 channels, membrane surface charge, neurotoxicity
- MeSH terms
- Action Potentials, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Fluorocarbons, Membrane Potentials, Purkinje Cells, Rats, Wistar, Alkanesulfonic Acids, Rats
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
