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-gat ed ion channels of neuronal cells isolated from fetal forebrain cortex and cultured for 6-14 days. Under the whole-cell voltage clamp, thiam ine tetrahydrofurfuryl disulfide (TTFD), a membrane-permeable derivati ve of thiamine, inhibited the delayed rectifier K+ current (I-K) in a concentration-dependent manner (10(-4)-10(-3) M). The I-K-suppressing effect was also observed by internal perfusion with 1 mM thiamine, but not by the external application of thiamine, indicating the poor perm eability of thiamine through the cell membrane. However, thiamine whic h was applied directly to the intracellular side of patch membranes in the inside-out configuration failed to decrease the open probability of the single I-K channel. In contrast, thiamine diphosphate decreased both the open probability and the open-time of the channel without ch anging the single channel conductance. These results suggest that phos phorylated thiamine can function as an endogenous K+ channel blocker i n neuronal cells. TTFD, when applied extracellularly at a concentratio n of 1 mM, prolonged the action potential (AP) duration of neurons (17 2.8 +/- 6.6%) without changing the resting membrane potential or AP am plitude, while the same concentration of thiamine did not influence an y parameters of the AP, implying that TTFD may cause the potentiation of neuronal AP through the inhibition of I-K. (C) 1998 Elsevier Scienc e Ltd. All rights reserved.