Somatostatin activates two types of inwardly rectifying K+ channels in MIN-6 cells

摘要

class="enumerated" style="list-style-type:decimal">Western blotting revealed the presence of five somatostatin receptor types, sst1, sst2, sst3, sst4 and sst5, in the mouse pancreatic β-cell line MIN-6.In MIN-6 cells, glucose-induced electrical activity was potently (pEC50= 12.7) and irreversibly reduced by somatostatin (SRIF-14); this was associated with hyperpolarization of the membrane potential (pEC50= 11.2) and a decrease in the input resistance (pEC50= 12.7).The effects of SRIF-14 were mimicked by 100 nm L-362,855 (a partial agonist at sst5 receptors), but not BIM-23027 or NNC-26,9100 (selective agonists at sst2 and sst4 receptors, respectively). CH-275 at 100 nm (a selective agonist at sst1 receptors) partially inhibited electrical activity but without membrane potential hyperpolarization.One hundred nanomolar SRIF-28 activated an inwardly rectifying K⁺ current (ISRIF). ISRIF was activated neither by 1 μm BIM-23056 nor CYN-154806 (antagonists at sst5 and sst2 receptors, respectively). The activation of I_SRIF by 100 nm SRIF-28 was, however, inhibited 93 % by BIM-23056; CYN-154806 had no effect.Both 100 nm glibenclamide and 200 μm tolbutamide, blockers of the β-cell ATP-sensitive K⁺ channel (K-ATP), reduced I_SRIF by ≈44 %, whereas 1 mm Ba²⁺ abolished I_SRIF.In cell-attached patches, 100 nm SRIF-14 activated two types of single-channel currents whose properties were consistent with those of K-ATP and GIRK channels.In conclusion, somatostatin can inhibit glucose-induced electrical activity in MIN-6 cells by the combined activation of K-ATP and GIRK channels. Studies with selective agonists and antagonists are consistent with this effect being mediated by the sst₅ receptor.