Reversible activation of the ATP-dependent potassium current with dialysis of frog atrial cells by micromolar concentrations of GDP

Summary

We studied the effects of internal and external solutions on potassium currents in frog atrial cells. Experiments were carried out in whole cell recording in the presence of tetrodotoxin and cobalt in the bath to suppress the inward currents. In the absence of pyruvate and glucose in the external solution, a time-independent current increased progressively in a few minutes till the death of the cell. This current had the properties of the ATP-sensitive potassium current IK(ATP) in mammalian cells. In the presence of pyruvate and glucose in the external solution, the membrane current stayed low for 30 min. Addition of guanosine monophosphate (GMP, 40 μm), guanosine triphosphate (GTP, 40 to 1000 μm), adenosine diphosphate (ADP, 40 μm) or adenosine triphosphate (ATP, 3000 μm) to the internal solution had no major effect on the current amplitude. In contrast, addition of GDP (20 or 40 μm) produced a loss of rectification in a few minutes. The current activated by GDP was time independent as was the current observed in the absence of glucose and pyruvate. It was sensitive to cesium and barium, it was blocked when ATP was added to GDP in the internal solution, and it was suppressed by the sulphonylurea glibenclamide (1 μm). We suggest that GDP produced a local depletion of ATP, by displacement of the equilibrium between ATP, GDP, ADP and GTP. This hypothesis is supported by the fact that the current activated by GDP was rapidly suppressed when adding GTP in excess to the internal solution.