INHIBITION OF THE DELAYED RECTIFIER K CURRENT IN GUINEA-PIG CARDIOMYOCYTES BY THIAMINE TETRAHYDROFURFURYL DISULFIDE

We examined effect of thiamine tetrahydrofurfuryl disulfide on electro physiological characteristics of single atrial myocytes, obtained by d igestion of guinea-pig heart, using collagenase. Membrane potential an d ion channel current in the atrial myocytes were recorded by the patc h clamp method. Thiamine tetrahydrofurfuryl disulfide prolonged action potentials at cycle lengths from 250 to 10,000 ms. The degree of thia mine tetrahydrofurfuryl disulfide-induced prolongation was similar amo ng these cycle lengths. Thiamine tetrahydrofurfuryl disulfide inhibite d the delayed rectifier K+ current, without affecting Ca2+ current and inward-rectifier K+ current. Thiamine tetrahydrofurfuryl disulfide bl ocked the delayed rectifier K+ current in voltage-and time-independent manner, indicating that thiamine tetrahydrofurfuryl disulfide blocked both subtypes of the delayed rectifier K+ current (rapid and slow com ponents). Thiamine, the parent molecule of thiamine tetrahydrofurfuryl disulfide, blocked the delayed rectifier K+ current only when thiamin e was applied intracellularly. Thiamine tetrahydrofurfuryl disulfide m ay be converted to thiamine in the cytoplasm, and then may block the t he delayed rectifier K+ channel from the intracellular side. Although thiamine tetrahydrofurfuryl disulfide (or thiamine) has some of the pr operties of class III antiarrhythmics agents, thiamine tetrahydrofurfu ryl disulfide did not exhibit reverse use-dependent prolongation of ac tion potential.