Glibenclamide, membrane depolarization

Membrane Potential. As early as 1970 Matthews and Dean reported depolarization of the B-cell by tolbutamide and glibenclamide. This observation was confirmed by others. Thus, in the presence of a nonstimulating glucose concentration (3 mM), tolbutamide and glibenclamide produced depolarization and spike activity (Meissner and Atwater, 1976 Meissner et al., 1979 Henquin and Meissner, 1982). These effects were not due to Na+ influx (Kawazu et al., 1980). 

Ca2+ Fluxes. As can be expected, sulphonylureas increase net Ca2+ uptake along voltage-dependent Ca2+ channels (Henquin, 1980b Ammon et al., 1986) and, as far as the chemical structure is concerned, only those sulphonylureas that produce insulin release enhance uptake of Ca2+ (Heilman, 1981). Uptake of Ca2+ is associated with increased [Ca2+]j (Abrahamson et al., 1985). In HIT cells, membrane depolarization effected by the addition of glibenclamide or tolbutamide increased intracellular Ca2+ by activating voltage-dependent Ca2+ channels (Nelson et al., 1987). 

Figure 3 Effects of various stimuli and mitochondrial inhibitors on the resting membrane potential of quiescent chromaffin cells. A typical example of hypoxia-induced membrane depolarization is shown in (a), using nystatin perforated-patch whole-cell recording. In (b), bicuculline (100 pM), a reversible inhibitor of small-conductance Ca +-dependent K+ channels (SK), also caused membrane depolarization similar to hypoxia. The mitochondrial inhibitors 2,4-drnitrophenol (DNP) and cyanide (CN) did not mimic the h poxia-mduced membrane depolarization seen in (c) and (d), respectively in fact, in (d), CN caused membrane h3q)erpolarization, though in most cases no change in membrane potential was observed. Both DNP and CN were usually without effect even after perfusing the drug for >10 min. In (e), the hyperpolarizing effect of CN was reversed in the presence of 200 pM glibenclamide, a blocker of Katp channels.

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