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NaCN (100 \u00b5M) exposure for 10 min significantly decreased contraction and intracellular Ca<jats:sup>2+<\/jats:sup>concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) transient amplitudes, systolic but not diastolic [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, and maximal L-type Ca<jats:sup>2+<\/jats:sup>current ( I<jats:sub>Ca<\/jats:sub>) amplitude, indicating acute alteration of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>homeostasis largely accounted for the observed excitation-contraction abnormalities. In addition, NaCN depolarized resting membrane potential ( E<jats:sub>m<\/jats:sub>), reduced action potential (AP) amplitude, prolonged AP duration at 50% (APD<jats:sub>50<\/jats:sub>) and 90% repolarization (APD<jats:sub>90<\/jats:sub>), and suppressed depolarization-activated K<jats:sup>+<\/jats:sup>currents but had no effect on Na<jats:sup>+<\/jats:sup>-Ca<jats:sup>2+<\/jats:sup>exchange current ( I<jats:sub>NaCa<\/jats:sub>). NaCN did not affect cellular adenosine triphosphate levels but depolarized mitochondrial membrane potential (\u0394\u03a8<jats:sub>m<\/jats:sub>) and increased superoxide (O<jats:sub>2<\/jats:sub><jats:sup>\u00b7\u2212<\/jats:sup>) levels. Methylene blue (MB; 20 \u00b5g\/ml) added 3 min after NaCN restored contraction and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>transient amplitudes, systolic [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, E<jats:sub>m<\/jats:sub>, AP amplitude, APD<jats:sub>50<\/jats:sub>, APD<jats:sub>90<\/jats:sub>, I<jats:sub>Ca<\/jats:sub>, depolarization-activated K<jats:sup>+<\/jats:sup>currents, \u0394\u03a8<jats:sub>m<\/jats:sub>, and O<jats:sub>2<\/jats:sub><jats:sup>\u00b7\u2212<\/jats:sup>levels toward normal. We conclude that MB reversed NaCN-induced cardiotoxicity by preserving intracellular Ca<jats:sup>2+<\/jats:sup>homeostasis and excitation-contraction coupling ( I<jats:sub>Ca<\/jats:sub>), minimizing risks of arrhythmias ( E<jats:sub>m<\/jats:sub>, AP configuration, and depolarization-activated K<jats:sup>+<\/jats:sup>currents), and reducing O<jats:sub>2<\/jats:sub><jats:sup>\u00b7\u2212<\/jats:sup>levels.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY Cyanide poisoning due to industrial exposure, smoke inhalation, and bioterrorism manifests as cardiogenic shock and requires rapidly effective antidote. In the early stage of cyanide exposure, adenosine triphosphate levels are normal but myocyte contractility is reduced, largely due to alterations in Ca<jats:sup>2+<\/jats:sup>homeostasis because of changes in oxidation-reduction environment of ion channels. Methylene blue, a drug approved by the U.S. Food and Drug Administration, ameliorates cyanide toxicity by normalizing oxidation-reduction state and Ca<jats:sup>2+<\/jats:sup>channel function.<\/jats:p>","DOI":"10.1152\/japplphysiol.00967.2017","type":"journal-article","created":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T19:54:07Z","timestamp":1518119647000},"page":"1164-1176","source":"Crossref","is-referenced-by-count":22,"title":["Methylene blue counteracts cyanide cardiotoxicity: cellular mechanisms"],"prefix":"10.1152","volume":"124","author":[{"given":"Joseph Y.","family":"Cheung","sequence":"first","affiliation":[{"name":"Center of Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania"},{"name":"Department of Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, 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