Activation of M2-M8P by ADPR and regulation by extracellular Ca2+. A and B, whole-cell (w.c.) currents of cells expressing M2-M8P and wild-type TRPM2, respectively, elicited by infusion of 0.6 mm ADPR through the patch pipette. Each example represents four to five similar experiments. The Ca2+ concentration of the pipette solution was buffered with EGTA to below 10 nm. Horizontal black bars indicate time periods during which the standard bath solution (1.2 mm Ca2+) was exchanged with either a divalent cation-free solution (DVF) or a solution containing NMDG as the main extracellular cation. C and D, I-V relations of currents shown in A and B, respectively, obtained during voltage ramps from −90 to +60 mV from a holding potential of −60 mV.