ATP-sensitive K+ channels that are blocked by hypoglycemia-inducing sulfonylureas in insulin-secreting cells are activated by galanin, a hyperglycemia-inducing hormone.
The action of the hyperglycemia-inducing hormone galanin, a 29-amino acid peptide named from its N-terminal glycine and C-terminal amidated alanine, was studied in rat insulinoma (RINm5F) cells using electrophysiological and 86Rb+ flux techniques. Galanin hyperpolarizes and reduces spontaneous electrical activity by activating a population of ATP-sensitive K+ channels with a single-channel conductance of 30 pS (at -60 mV). Galanin-induced hyperpolarization and reduction of spike activity are reversed by the hypoglycemia-inducing sulfonylurea glibenclamide. Glibenclamide blocks the galanin-activated ATP-sensitive K+ channel. 86Rb+ efflux from insulinoma cells is stimulated by galanin in a dose-dependent manner. The half-maximum value of activation is found at 1.6 nM. Galanin-induced 86Rb+ efflux is abolished by glibenclamide. The half-maximum value of inhibition is found at 0.3 nM, which is close to the half-maximum value of inhibition of the ATP-dependent K+ channel reported earlier. 86Rb+ efflux studies confirm the electrophysiological demonstration that galanin activates an ATP-dependent K+ channel.
D000200:Action Potentials / Q000187:drug effects; D007516:Adenoma, Islet Cell / Q000473:pathology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004347:Drug Interactions; D019004:Galanin; D005905:Glyburide / Q000494:pharmacology*; D007340:Insulinoma / Q000473:pathology*; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D012413:Rubidium / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007473:Ion Channels; D010455:Peptides; D010566:Virulence Factors, Bordetella; D019004:Galanin; D000255:Adenosine Triphosphate; D012413:Rubidium; D011188:Potassium; D005905:Glyburide; D002118:Calcium