第68回生態適応セミナー (Bセミナー)

     
 

日時:3月15日(木曜日)16:00 –

 
  場所:片平キャンパス プロジェクト総合研究棟 講義室105  
     

Thomas Zimmer 博士(University Hospital Jena)

     
  Effects of the Fugu Poison Tetrodotoxin (TTX) on the Mammalian Cardiovascular System  
     
 

The Fugu poison, tetrodotoxin (TTX), is a highly specific blocker of voltage-gated Na+ channels. The human genome encodes nine functional Na+ channels. The major cardiac isoform, namely Nav1.5, is resistant to nanomolar concentrations of TTX (IC50 >= 1 µM). In contrast, the isoforms of the skeletal muscle and nervous system, Nav1.1-Nav1.4, are TTX sensitive (TTXs; IC50 ~ 10 nM). During the last two decades, it has become evident that in addition to the major cardiac isoform Nav1.5, several of the TTXs isoforms are expressed in the mammalian heart. Respective data resulted in far-reaching speculations on the function of these additional Na+ channels in the human heart. Most of these conclusions were drawn from immunohistochemical and electrophysiological assays using heart cells of small rodents. We analysed the Na+ channel mRNA pattern in the heart of various mammalian species and found only minute quantities of transcripts for TTXs Na+ channels in the whole human heart, suggesting that TTXs Na+ channels are not involved in cardiac excitation phenomena in humans. This conclusion is strongly supported by previous data from TTX-intoxicated mammalian animals and from cases of human tetrodotoxication where the drug caused at most little alterations of the cardiac output and of the patients' electrocardiograms (ECG). In contrast, TTX had dramatic effects on nerve conduction and skeletal/smooth muscle contractions, finally resulting in a life-threatening reduction of respiratory parameters and in a severe drop of the arterial blood pressure.