Effects of ADP upon the ATP-sensitive K⁺ channel in rat ventricular myocytes

Summary

The effects of ADP upon the gating of ATP-sensitive K⁺ channels from rat ventricular myocytes have been investigated by patch-clamp single-channel current recording experiments. ADP was applied to the internal surface of excised insideout membrane patches and depending upon the experimental protocol and the concentration it was found that ADP could either inhibit or stimulate openings of ATP-sensitive K⁺ channels. In the absence of inactivation, ATP-sensitive K⁺ channels were inhibited by ADP in a dose-dependent manner. Partially inactivated channels, on the other hand, were stimulated by low (10 to 250 μM) and inhibited by high (>250 μM) concentrations of ADP. ATP-sensitive K⁺ channels which were being inhibited by ATP (<1 mM) could be opened by the simultaneous application of ADP (50 μM to 1 mM). ADP had no effect upon channels inhibited by mM concentrations of ATP. The situation was further complicated when it was found that inhibition evoked by ADP was strongly attenuated by the presence of Mg²⁺ ions whilst channel stimulation, whether of partially inactivated channels or channels inhibited by ATP, required the presence of Mg²⁺ ions. The analog of ADP, ADPβS, always evoked inhibition of ATP-sensitive K⁺ channels which was not affected by the presence or absence of Mg²⁺ ions.