GTP and GDP activation of K+ channels that can be inhibited by ATP

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 M – 1 mM) and GDP (100 M 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.