Thiamine and its derivatives inhibit delayed rectifier potassium channels of rat cultured cortical neurons.
We examined the effects of thiamine and its derivatives on voltage-gated ion channels of neuronal cells isolated from fetal forebrain cortex and cultured for 6-14 days. Under the whole-cell voltage clamp, thiamine tetrahydrofurfuryl disulfide (TTFD), a membrane-permeable derivative of thiamine, inhibited the delayed rectifier K+ current (IK) in a concentration-dependent manner (10(-4)-10(-3) M). The IK-suppressing effect was also observed by internal perfusion with 1 mM thiamine, but not by the external application of thiamine, indicating the poor permeability of thiamine through the cell membrane. However, thiamine which was applied directly to the intracellular side of patch membranes in the inside-out configuration failed to decrease the open probability of the single IK channel. In contrast, thiamine diphosphate decreased both the open probability and the open-time of the channel without changing the single channel conductance. These results suggest that phosphorylated thiamine can function as an endogenous K+ channel blocker in neuronal cells. TTFD, when applied extracellularly at a concentration of 1 mM, prolonged the action potential (AP) duration of neurons (172.8 +/- 6.6%) without changing the resting membrane potential or AP amplitude, while the same concentration of thiamine did not influence any parameters of the AP, implying that TTFD may cause the potentiation of neuronal AP through the inhibition of IK.
Houzen
H
H
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan. hohzen@med.hokudai.ac.jp
Kanno
M
M
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005666:Fursultiamin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D051381:Rats; D017207:Rats, Sprague-Dawley; D013831:Thiamine / Q000494:pharmacology*; D013835:Thiamine Pyrophosphate / Q000494:pharmacology
D026902:Potassium Channel Blockers; D005666:Fursultiamin; D013835:Thiamine Pyrophosphate; D013831:Thiamine