K+ channels that can be inhibited by intracellular ATP have been found in many different cell types. In the insulin-secreting pancreatic islet cells these channels are of crucial importance for stimulus-secretion coupling as glucose stimulation closes the ATP-sensitive channels which leads to depolarization and firing of Ca2+ action potentials. We now demonstrate that nucleotides other than ATP also influence the gating of these K+ channels. In contrast to the action of ATP, GTP (10 μM – 1 mM) and GDP (100 μM to 1 mM) evoke dose-dependent channel activation and this effect is immediately reversible. Phosphorylation is not directly involved as non-hydrolysable GTP-and GDP-analogues also evoke channel opening. ATP reversibly inhibits opening of the GTP- or GDP- activated K+ channels.
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