ASCORBIC-ACID MODULATION OF CALCIUM CHANNELS IN PANCREATIC BETA-CELLS

We have studied the effect of ascorbic acid on voltage-dependent calci um channels in pancreatic beta cells. Using the whole-cell and perfora ted-patch variants of the patch clamp technique to record calcium tail currents, we have shown that the slowly deactivating (SD) calcium cha nnel, which is similar to the T-type channel in other cells, is inhibi ted in a voltage-dependent manner by ascorbic acid (AA). The other cha nnels that carry inward current in beta 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 whi ch can be explained by the hypothesis that approximately 50-60% of the channels have their voltage dependence shifted by approximately 62 mV in the depolarizing direction. Thus, ascorbate appears to modify only a fraction of the SD channels. The activation kinetics of the ascorba te-modified channels are slower than control channels in a manner that is consistent with this hypothesis. Deactivation and inactivation kin etics are unaffected by ascorbate. These effects of ascorbate require metal ions, and it appears that some of the activity of ascorbate is d ue to a product of its metal catalyzed oxidation, perhaps dehydroascor bate.