FIGURE 3.
Inhibition of wild-type TRPM2 and M2-M8P by divalent cation-free extracellular solution but in the presence of 1 μm intracellular Ca2+. A and B, whole-cell (w.c.) currents of cells expressing M2-M8P and wild-type TRPM2, respectively. Each example represents four to six similar experiments. Currents were elicited by infusion of ADPR (0.05 mm) and Ca2+ (1 μm) through the patch pipette. The holding potential was −30 mV to attenuate the large currents. Note the delayed response of current inhibition during Ca2+ depletion and the renewed current development during replenishment of extracellular Ca2+. The kinetics of inhibition were analyzed and are reported in text. 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.