A NON-COFACTOR ROLE OF THIAMINE DERIVATIVES IN EXCITABLE CELLS

Thiamine diphosphate (TDP) is an important cofactor of pyruvate (PDH) and alpha-ketoglutarate (KGDH) dehydrogenases and transketolase. Thiam ine deficiency leads to reversible and irreversible brain lesions due to impaired oxidative metabolism. A specific non-cofactor role for thi amine has also been proposed in excitable cells and thiamine triphosph ate (TTP) might be involved in the regulation of ion channels. Thiamin e is taken up by neuroblastoma cells through a high affinity transport er. Inside the cells, it is rapidly phosphorylated to TDP. This high t urnover TDP pool is the precursor for TTP. Most of the TDP however has a low turnover and is associated with PDH and KGDH in mitochondria. I n excised inside-out patches from neuroblastoma cells, TTP, at a conce ntration of 1 mu M, activates chloride channels of large unitary condu ctance, the so-called maxi-Cl- channels. These channels are inhibited by oxythiamine from the outide. In addition to the role of TTP in the regulation of chloride channels, thiamine itself or a presently unknow n analog, may have trophic effects on neuronal cells.