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

Paul A. Smith, Lynda A. Sellers and Patrick P. A. Humphrey

1. Western blotting revealed the presence of five somatostatin receptor types, sst₁, sst₂, sst₃, sst₄ and sst₅, in the mouse pancreatic -cell line MIN-6.

2. 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).

3. 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.

4. One hundred nanomolar SRIF-28 activated an inwardly rectifying K⁺ current (I_SRIF) I_SRIF was activated neither by 1 M 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.

5. Both 100 nM glibenclamide and 200 M tolbutamide, blockers of the -cell ATP-sensitive K⁺ channel (K-ATP), reduced I_SRIF by ~44 %, whereas 1 mM Ba²⁺ abolished I_SRIF.

6. 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.

7. 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.

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