Sulfonylurea receptors and ATP-sensitive K⁺ channels in clonal pancreatic α cells. Evidence for two high affinity sulfonylurea receptors

We tested for the presence of sulfonylurea receptors in pancreatic α cells. Two high affinity sulfonylurea receptors were identified in clonal pancreatic α cells (αTC-6): a 140-kDa species observed previously in clonal pancreatic β cells (HIT) and a second 150-kDa protein. The dissociation constant (K(d)) for both receptors is ~3.5 nM for an iodinated glyburide analog, 5-iodo-2-hydroxyglyburide. The estimated number of receptors (B(max)) increases approximately 2-fold, from 3.1 to 6.8 pmol/mg of membrane protein as the pH of the binding buffer is reduced from 7.5 to 6. Consistent with the notion that high affinity sulfonylurea receptors are integral components of the ATP-sensitive K⁺ channel, we demonstrated the presence of ATP-sensitive K⁺ channels in inside-out patches of αTC-6 cells. Whole cell K⁺ currents that activated with time showed inward rectification at positive potentials (above 0 mV) and were almost completely suppressed by 5 nM glyburide. Likewise, glyburide blocked ⁸⁶Rb⁺ efflux from ATP-depleted αTC-6 cells, an effect that was reversed by 400 μM diazoxide. The presence of sulfonylurea receptors provides a mechanism by which sulfonylureas can directly modulate α cell function. The properties of the 150-kDa receptor and the role of ATP-sensitive K⁺ channels in α cells remain to be elucidated, but as in β cells, ATP-sensitive K⁺ channels may be involved in metabolic regulation of α cells by glucose.