Intracellular ATP modifies the voltage dependence of the fast transient outward K+ current in Lymnaea stagnalis neurones.

1. The action of intracellular ATP on the fast transient outward K+ current (A-current) was studied in dialysed voltage-clamped Lymnaea stagnalis neurones. 2. When introduced intracellularly in millimolar concentrations ATP caused a shift of the steady-state inactivation curve along the voltage axis in the direction of positive potentials and decreased A-current at all test voltages. 3. Intracellular treatment with an inhibitor of ATP synthesis, sodium arsenate, led to the opposite changes. The action of arsenate was not reversed upon its removal. After wash-out of arsenate ATP restored the initial voltage dependence. 4. Addition of Mg2+ to the solution weakened the action of ATP in proportion to the Mg2+: ATP concentration ratio. On the other hand, in neurones pretreated with arsenate, Mg2+ did not affect the ATP action. 5. When a mixture of glycolytic substrates was applied after arsenate wash-out the activation and inactivation curves shifted towards positive voltages. A substrate of oxidative phosphorylation was ineffective in the same conditions. 6. Non-hydrolysable analogues of ATP, adenosine-5'-O-gamma-thiotriphosphate and adenylyl imidodiphosphate, did not mimic the ATP action. This means that the ATP effect is mediated by some enzymatic process(es). 7. Elevation of total cytosolic Ca2+ concentration as well as intracellular application of agents increasing intracellular free Ca2+ reduced A-current amplitude but failed to alter its voltage dependence. Therefore, ATP action cannot be related to activation of Ca2+ transport. 8. Treatment of the neurones with alkaline phosphatase evoked a shift of the inactivation voltage dependence towards hyperpolarizing potentials and increased the A-current amplitudes at all test voltages. 9. The data indicate that a change in intracellular ATP concentration modulates the A-current voltage dependence. The effect of ATP is probably the result of phosphorylation of a channel protein or some associated proteins, but lowering of free Mg2+ concentration cannot be excluded. The possible physiological significance of the phenomenon is discussed.