ADPR affinity for channel activation is intact for nvTRPM2 channels lacking the NUDT9-H domain.
(A–C) Macroscopic inward Na+ currents at −20 mV membrane potential activated by cytosolic exposure to various concentrations of ADPR (gray bars) plus 125 µM Ca2+ (black bars) recorded from inside-out patches excised from Xenopus oocytes preinjected with cRNA encoding full-length (A), 1208STOP (B), or 1242STOP (C) nvTRPM2. (D) Steady-state currents in the presence of test [ADPR], normalized to the mean of the currents during bracketing exposures of the same patch to saturating (100–1,000 µM) ADPR, plotted as a function of [ADPR] for full-length (dark blue symbols), 1208STOP (red symbols), and 1242STOP (yellow symbols) nvTRPM2. Data represent mean ± SEM from 3 to 32 independent experiments. Fits to the Hill equation (colored lines) yielded fit parameters of EC50 = 2.3 ± 0.2 µM, nH = 1.4 ± 0.1 for full-length; EC50 = 4.2 ± 0.6 µM, nH = 1.2 ± 0.2 for 1208STOP; and EC50 = 7.4 ± 0.7 µM, nH = 1.3 ± 0.1 for 1242STOP nvTRPM2.