{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:24:58Z","timestamp":1783337098460,"version":"3.54.6"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T00:00:00Z","timestamp":1371168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Tetrodotoxin (TTX) is believed to be one of the most selective inhibitors  of voltage-gated fast Na+ channels in excitable tissues. Recently, however, TTX has been shown to block L-type Ca2+ current (ICa) in canine cardiac cells. In the present study, the TTX-sensitivity of ICa was studied in isolated canine ventricular myocytes as a function of (1) channel phosphorylation, (2) extracellular pH and (3) the redox potential of the bathing medium using the whole cell voltage clamp technique. Fifty-five micromoles of TTX (IC50 value obtained under physiological conditions) caused 60% \u00b1 2% inhibition of ICa in acidic (pH = 6.4), while only a 26% \u00b1 2% block in alkaline (pH = 8.4) milieu. Similarly, the same concentration of TTX induced 62% \u00b1 6% suppression of ICa in a reductant milieu (containing glutathione + ascorbic acid + dithiothreitol, 1 mM each), in contrast to the 31% \u00b1 3% blockade obtained in the presence of a strong oxidant (100 \u03bcM H2O2). Phosphorylation of the channel protein (induced by 3 \u03bcM forskolin) failed to modify the inhibiting potency of TTX; an IC50 value of 50 \u00b1 4 \u03bcM was found in forskolin. The results are in a good accordance with the predictions of our model, indicating that TTX binds, in fact, to the selectivity filter of cardiac L-type Ca channels.<\/jats:p>","DOI":"10.3390\/md11062140","type":"journal-article","created":{"date-parts":[[2013,6,14]],"date-time":"2013-06-14T11:47:47Z","timestamp":1371210467000},"page":"2140-2153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Tetrodotoxin Blockade on Canine Cardiac L-Type Ca2+ Channels Depends on pH and Redox Potential"],"prefix":"10.3390","volume":"11","author":[{"given":"Bence","family":"Hegyi","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Kom\u00e1romi","sequence":"additional","affiliation":[{"name":"Clinical Research Center and Thrombosis Haemostasis and Vascular Biology Research Group of the Hungarian Academy of Sciences, University of Debrecen, P.O. Box 40, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korn\u00e9l","family":"Kistam\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Ruzsnavszky","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"V\u00e1czi","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Magyar","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"B\u00e1ny\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"N\u00e1n\u00e1si","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"},{"name":"Department of Dental Physiology and Pharmacology, Medical and Health Science Center,  University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Szentandr\u00e1ssy","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"},{"name":"Department of Dental Physiology and Pharmacology, Medical and Health Science Center,  University of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/263344a0","article-title":"Voltage-dependent action of tetrodotoxin in mammalian cardiac muscle","volume":"263","author":"Baer","year":"1976","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1113\/jphysiol.1981.sp013879","article-title":"Sodium current in single rat heart muscle cells","volume":"318","author":"Brown","year":"1981","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.3390\/md9112409","article-title":"Tetrodotoxin sensitivity of the vertebrate cardiac Na+ current","volume":"9","author":"Vornanen","year":"2011","journal-title":"Mar. 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