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Somatostatin activates two types of inwardly rectifying K + channels in MIN‐6 cells
Author(s) -
Smith Paul A.,
Sellers Lynda A.,
Humphrey Patrick P. A.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0127g.x
Subject(s) - g protein coupled inwardly rectifying potassium channel , hyperpolarization (physics) , somatostatin , somatostatin receptor , agonist , receptor , medicine , endocrinology , pertussis toxin , chemistry , membrane potential , potassium channel , g protein , tolbutamide , glibenclamide , biophysics , biology , biochemistry , insulin , stereochemistry , nuclear magnetic resonance spectroscopy , diabetes mellitus
1 Western blotting revealed the presence of five somatostatin receptor types, sst 1 , sst 2 , sst 3 , sst 4 and sst 5 , in the mouse pancreatic β‐cell line MIN‐6. 2 In MIN‐6 cells, glucose‐induced electrical activity was potently (pEC 50 = 12.7) and irreversibly reduced by somatostatin (SRIF‐14); this was associated with hyperpolarization of the membrane potential (pEC 50 = 11.2) and a decrease in the input resistance (pEC 50 = 12.7). 3 The effects of SRIF‐14 were mimicked by 100 n m L‐362,855 (a partial agonist at sst 5 receptors), but not BIM‐23027 or NNC‐26,9100 (selective agonists at sst 2 and sst 4 receptors, respectively). CH‐275 at 100 n m (a selective agonist at sst 1 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 μ m BIM‐23056 nor CYN‐154806 (antagonists at sst 5 and sst 2 receptors, respectively). The activation of I SRIF by 100 n m SRIF‐28 was, however, inhibited 93 % by BIM‐23056; CYN‐154806 had no effect. 5 Both 100 n m glibenclamide and 200 μ m tolbutamide, blockers of the β‐cell ATP‐sensitive K + channel (K‐ATP), reduced I SRIF by ≈44 %, whereas 1 m m Ba 2+ abolished I SRIF . 7 In cell‐attached patches, 100 n m SRIF‐14 activated two types of single‐channel currents whose properties were consistent with those of K‐ATP and GIRK channels. 8 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 sst 5 receptor.