Intracellular ADP-ribose inhibits ATP-sensitive K⁺ channels in rat ventricular myocytes

Cyclic ADP-ribose (cADPR), an NAD metabolite, has been shown to be a messenger for Ca²⁺ mobilization from intracellular Ca²⁺ stores. However, the physiological role of ADP-ribose (ADPR), another metabolite of NAD, is not known. We examined the effects of cADPR and ADPR on the ATP-sensitive K⁺ channel (K(ATP)) activity in rat ventricular myocytes by use of the inside- out patch-clamp configuration. ADPR, but not cADPR, inhibited the channel activity at micromolar range with an inhibitor constant (K(i)) of 38.4 μM. The Hill coefficient was 0.9. ATP inhibited the K⁺ channel with a K(i) of 77.8 μM, and the Hill coefficient was 1.8. Single-channel conductance was not affected by ADPR. These findings strongly suggest that ADPR may act as a regulator of K(ATP) channel activity.