{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:57:47Z","timestamp":1761058667634},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,4,25]],"date-time":"2007-04-25T00:00:00Z","timestamp":1177459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ceramides are novel second messengers that may mediate signaling leading to apoptosis and the regulation of cell cycle progression. Moreover, ceramide analogs have been reported to directly modulate K<jats:sup>+<\/jats:sup> and Ca<jats:sup>2+<\/jats:sup> channels in different cell types. In this report, the effect of C<jats:sub>6<\/jats:sub>\u2010ceramide on the voltage\u2010gated inward Na<jats:sup>+<\/jats:sup> currents (I<jats:sub>Na<\/jats:sub>) in cultured rat myoblasts was investigated using whole\u2010cell current recording and a fluorescent Ca<jats:sup>2+<\/jats:sup> imaging experiment. At concentrations of 1\u2013100 \u00b5M, ceramide produced a dose\u2010independent and reversible inhibition of I<jats:sub>Na<\/jats:sub>. Ceramide also significantly shifted the steady\u2010state inactivation curve of I<jats:sub>Na<\/jats:sub> by 16 mV toward the hyperpolarizing potential, but did not alter the steady\u2010state activation properties. C<jats:sub>2<\/jats:sub>\u2010ceramide caused a similar inhibitory effect on I<jats:sub>Na<\/jats:sub> amplitude. However, dihydro\u2010C<jats:sub>6<\/jats:sub>\u2010ceramide, the inactive analog of ceramide, failed to modulate I<jats:sub>Na<\/jats:sub>. The effect of C<jats:sub>6<\/jats:sub>\u2010ceramide on I<jats:sub>Na<\/jats:sub> was abolished by intracellular infusion of the Ca<jats:sup>2+<\/jats:sup>\u2010chelating agent BAPTA, but was mimicked by application of caffeine. Blocking the release of Ca<jats:sup>2+<\/jats:sup> from the sarcoplasmic reticulum with xestospongin C or heparin, an inositol 1,4,5\u2010trisphosphate (IP<jats:sub>3<\/jats:sub>) receptor blocker, induced a gradual increase in I<jats:sub>Na<\/jats:sub> amplitude and eliminated the effect of ceramide on I<jats:sub>Na<\/jats:sub>. In contrast, ruthenium red, which is a blocker of the ryanodine\u2010sensitive Ca<jats:sup>2+<\/jats:sup> receptor did not affect the action of C<jats:sub>6<\/jats:sub>\u2010ceramide on I<jats:sub>Na<\/jats:sub>. Intracellular application of the G\u2010protein agonist GTP\u03b3S also induced a gradual decrease in I<jats:sub>Na<\/jats:sub> amplitude, while the G\u2010protein antagonist GDP\u03b2S eliminated the effect of C<jats:sub>6<\/jats:sub>\u2010ceramide on I<jats:sub>Na<\/jats:sub>. Calcium imaging showed that C<jats:sub>6<\/jats:sub>\u2010ceramide could give rise to a significant elevation of intracellular calcium. Our data show that increased calcium release through the IP<jats:sub>3<\/jats:sub>\u2010sensitive Ca<jats:sup>2+<\/jats:sup> receptor, which probably occurred through the G\u2010protein and phospholipase C pathway, may be responsible for C<jats:sub>6<\/jats:sub>\u2010ceramide\u2010induced inhibition of the I<jats:sub>Na<\/jats:sub> of rat myoblasts. J. Cell. Physiol. 213: 151\u2013160, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21106","type":"journal-article","created":{"date-parts":[[2007,4,26]],"date-time":"2007-04-26T05:48:14Z","timestamp":1177566494000},"page":"151-160","source":"Crossref","is-referenced-by-count":8,"title":["C<sub>6<\/sub>\u2010ceramide inhibited Na<sup>+<\/sup> currents by intracellular Ca<sup>2+<\/sup> release in rat 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