Tohse N, Houzen H, Kanno M
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1998 May;357(5):540-7. doi: 10.1007/pl00005205.
We examined effect of thiamine tetrahydrofurfuryl disulfide on electrophysiological characteristics of single atrial myocytes, obtained by digestion of guinea-pig heart, using collagenase. Membrane potential and ion channel current in the atrial myocytes were recorded by the patch clamp method. Thiamine tetrahydrofurfuryl disulfide prolonged action potentials at cycle lengths from 250 to 10,000 ms. The degree of thiamine tetrahydrofurfuryl disulfide-induced prolongation was similar among these cycle lengths. Thiamine tetrahydrofurfuryl disulfide inhibited the delayed rectifier K+ current, without affecting Ca2+ current and inward-rectifier K+ current. Thiamine tetrahydrofurfuryl disulfide blocked 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 components). Thiamine, the parent molecule of thiamine tetrahydrofurfuryl disulfide, blocked the delayed rectifier K+ current only when thiamine was applied intracellularly. Thiamine tetrahydrofurfuryl disulfide may be converted to thiamine in the cytoplasm, and then may block the the delayed rectifier K+ channel from the intracellular side. Although thiamine tetrahydrofurfuryl disulfide (or thiamine) has some of the properties of class III antiarrhythmics agents, thiamine tetrahydrofurfuryl disulfide did not exhibit reverse use-dependent prolongation of action potential.
我们研究了呋喃硫胺对通过用胶原酶消化豚鼠心脏获得的单个心房肌细胞电生理特性的影响。采用膜片钳技术记录心房肌细胞的膜电位和离子通道电流。呋喃硫胺可使动作电位在250至10,000毫秒的心动周期长度范围内延长。在这些心动周期长度范围内，呋喃硫胺诱导的延长程度相似。呋喃硫胺抑制延迟整流钾电流，而不影响钙电流和内向整流钾电流。呋喃硫胺以电压和时间非依赖性方式阻断延迟整流钾电流，表明呋喃硫胺阻断了延迟整流钾电流的两种亚型（快速和慢速成分）。硫胺素是呋喃硫胺的母体分子，仅在细胞内应用硫胺素时才阻断延迟整流钾电流。呋喃硫胺可能在细胞质中转化为硫胺素，然后可能从细胞内侧阻断延迟整流钾通道。尽管呋喃硫胺（或硫胺素）具有一些III类抗心律失常药物的特性，但呋喃硫胺并未表现出动作电位的反向使用依赖性延长。
