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

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 inside-out 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 microM) and inhibited by high (greater than 250 microM) concentrations of ADP. ATP-sensitive K+ channels which were being inhibited by ATP (less than 1 mM) could be opened by the simultaneous application of ADP (50 microM 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, ADP beta S, always evoked inhibition of ATP-sensitive K+ channels which was not affected by the presence or absence of Mg2+ ions.