Ascorbic acid modulation of calcium channels in pancreatic β cells

We have studied the effect of ascorbic acid on voltage-dependent calcium channels in pancreatic β cells. Using the whole-cell and perforated-patch variants of the patch clamp technique to record calcium tail currents, we have shown that the slowly deactivating (SD) calcium channel, which is similar to the T-type channel in other cells, is inhibited in a voltage-dependent manner by ascorbic acid (AA). The other channels that carry inward current in β cells, FD calcium channels and sodium channels, are unaffected by AA. Ascorbic acid causes a voltage-dependent decrease in the magnitude of the SD channel conductance which can be explained by the hypothesis that ∼50-60% of the channels have their voltage dependence shifted by ∼62 mV in the depolarizing direction. Thus, ascorbate appears to modify only a fraction of the SD channels. The activation kinetics of the ascorbate-modified channels are slower than control channels in a manner that is consistent with this hypothesis. Deactivation and inactivation kinetics are unaffected by ascorbate. These effects of ascorbate require metal ions, and it appears that some of the activity of ascorbate is due to a product of its metal catalyzed oxidation, perhaps dehydroascorbate.