Excitatory effect of thiamin on CA1 pyramidal neurones in rat hippocampal slices in vitro.
Clinically, acute thiamin deficiency may lead to Wernicke encephalopathy and fulminant cardial beriberi. Both diseases respond to high parenteral doses of thiamin. The cofactor role of intracellular thiamin diphosphate has been thoroughly investigated, but an additional acute effect of unphosphorylated extracellular thiamin has been postulated but not elucidated. In order to investigate the role of thiamin at the membrane level in the central nervous system, a study using a well-established in vitro rat hippocampal slice model was designed. Hippocampal slices were perfused with 0.5, 0.75 and 1 mM thiamin solutions for 30 min and the pre-synaptic volley, field excitatory post-synaptic potential and population spike amplitudes were recorded continuously. The results showed an acute, excitatory effect of high-dose thiamin on hippocampal neurones by significantly increasing the number of repetitive afterdischarges. Additional experiments with low concentrations of the potassium channel blocker 4-aminopyridine showed similar findings. The results support previous evidence of thiamin affecting membrane ion channel activity, probably involving potassium channels, although the precise mechanisms of action are still unclear.
Tallaksen
C M
CM
Department of Neurology, Rikshospitalet, The National Hospital, 0027 Oslo, Norway.
Taubøll
E
E
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D013831:Thiamine / Q000494:pharmacology*
D015761:4-Aminopyridine; D013831:Thiamine