{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:01:05Z","timestamp":1791892865148,"version":"4.3.4"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,4,15]]},"abstract":"\n Our recent data show that in cardiac myocytes polyunsaturated fatty acids (PUFAs) are antiarrhythmic. They reduce\n I<\/jats:italic>\n Na<\/jats:sub>\n , shorten the action potential, shift the threshold for excitation to more positive potentials, and prolong the relative refractory period. In this study we use patch-clamp techniques in whole-cell mode and confocal Ca\n 2+<\/jats:sup>\n imaging to examine the effects of PUFAs on the voltage-gated L-type Ca\n 2+<\/jats:sup>\n current (\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n ), elementary sarcoplasmic reticulum Ca\n 2+<\/jats:sup>\n -release events (Ca\n 2+<\/jats:sup>\n -sparks), and [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n transients in isolated rat ventricular myocytes. Extracellular application of eicosapentaenoic acid (EPA; C20:5\n n<\/jats:italic>\n \u2212 3) produced a prompt and reversible concentration-dependent suppression of\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n . The concentration of EPA to produce 50% inhibition of\n I<\/jats:italic>\n Ca<\/jats:sub>\n was 0.8 \u03bcM in neonatal rat heart cells and 2.1 \u03bcM in adult ventricular myocytes. While the EPA induced suppression of\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n , it did not significantly alter the shape of the current\u2013voltage relation but did produce a small, but significant, negative shift of the steady-state inactivation curve. The inhibition of\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n was voltage- and time-dependent, but not use- or frequency-dependent. Other PUFAs, such as docosahexaenoic acid, arachidonic acid, linolenic acid, linoleic acid, conjugated linoleic acid, and eicosatetraynoic acid had similar effects on\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n as EPA. All-\n trans<\/jats:italic>\n -retinoic acid, which had been shown to suppress induced arrhythmogenic activity in rat heart cells, also produced a significant inhibition of\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n . The saturated stearic acid and the monounsaturated oleic acid had no effect on\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n . Because both\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n and sarcoplasmic reticulum Ca\n 2+<\/jats:sup>\n -release underlie many cardiac arrhythmias, we examined the effects of EPA on\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n and Ca\n 2+<\/jats:sup>\n -sparks. While EPA suppressed both, it did not change the temporal or spatial character of the Ca\n 2+<\/jats:sup>\n -sparks, nor did it alter the ability of\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n to trigger Ca\n 2+<\/jats:sup>\n -sparks. We conclude that PUFAs may act as antiarrhythmic agents\n in vivo<\/jats:italic>\n in normal and Ca\n 2+<\/jats:sup>\n -overloaded cells principally because they reduce Ca\n 2+<\/jats:sup>\n entry by blocking\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n . Furthermore, PUFAs act directly to decrease\n I<\/jats:italic>\n Na<\/jats:sub>\n and\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n , but indirectly to reduce the [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n transients and [Ca\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n -activated membrane current. Although a negative inotropic action is associated with application of PUFAs, it is clear that by reducing\n I<\/jats:italic>\n Ca,L<\/jats:sub>\n ,\n I<\/jats:italic>\n Na<\/jats:sub>\n and Ca\n 2+<\/jats:sup>\n -sparks, PUFAs can reduce spontaneous extrasystoles in the heart. The mechanisms by which PUFAs act are discussed.\n <\/jats:p>","DOI":"10.1073\/pnas.94.8.4182","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"4182-4187","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":303,"title":["Suppression of voltage-gated L-type Ca\n 2+<\/sup>\n currents by polyunsaturated fatty acids in adult and neonatal rat ventricular\u2009myocytes"],"prefix":"10.1073","volume":"94","author":[{"given":"Yong-Fu","family":"Xiao","sequence":"first","affiliation":[{"name":"The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Beth Israel Hospital, Boston, MA 02115; Massachusetts General Hospital, 13th Street, Charlestown, MA 02129; Department of Medicine, Harvard Medical School, Boston, MA 02215; and Departments of Molecular Biology and Biophysics and Physiology, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Gomez","sequence":"additional","affiliation":[{"name":"The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Beth Israel Hospital, Boston, MA 02115; Massachusetts General Hospital, 13th Street, Charlestown, MA 02129; Department of Medicine, Harvard Medical School, Boston, MA 02215; and Departments of Molecular Biology and Biophysics and Physiology, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Morgan","sequence":"additional","affiliation":[{"name":"The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Beth Israel Hospital, Boston, MA 02115; Massachusetts General Hospital, 13th Street, Charlestown, MA 02129; Department of Medicine, Harvard Medical School, Boston, MA 02215; and Departments of Molecular Biology and Biophysics and Physiology, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Beth Israel Hospital, Boston, MA 02115; Massachusetts General Hospital, 13th Street, Charlestown, MA 02129; Department of Medicine, Harvard Medical School, Boston, MA 02215; and Departments of Molecular Biology and Biophysics and Physiology, University of Maryland School of Medicine, Baltimore, MD 21201"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,4,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1139\/y85-232"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(92)90809-A"},{"key":"e_1_3_3_3_2","first-page":"H1518","volume":"259","author":"Hock C E","year":"1990","unstructured":"C E Hock, L D Beck, L C Bodine, D K Reibel Am J Physiol 259, H1518\u2013H1526 (1990).","journal-title":"Am J Physiol"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.10.4427"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)90828-3"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)92580-1"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530170043030"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.21.9886"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.9.3997"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.24.11000"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1978.sp012416"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.65.1.115"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235594"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7754384"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.270.1.C148"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199407000-00009"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.1.166"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(94)80677-0"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2446391"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199512000-00014"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb14704.x"},{"key":"e_1_3_3_22_2","first-page":"307","volume":"57","author":"Cohen C J","year":"1990","unstructured":"C J Cohen, T Bale, F Lei, M D Leibowitz Biophys J 57, 307, (abstr.). 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