PIP2 sensitivity of nvTRPM2 membrane interfacial cavity mutant channels. (A) Current amplitudes induced by ADPR (100 µM, black bar) of wild-type and mutant nvTRPM2 channels. PIP2 (green bars) dose-response recordings of nvTRPM2 R969A (II) (B), R1104A (III) (C) and R1114A (IV) (D) in presence of 100 µM ADPR (black bar). Since maximum currents were already observed in absence of external PIP2, natural PIP2 was scavenged via polylysine (15 µg/mL, PL, orange bar) and subsequently restored via increasing PIP2 concentrations. (E) Data summary of PIP2 sensitivity of mutants R969A (II), R1104A (III), and R1114A (IV) showing dominant right shift compared with wild-type nvTRPM2. Data represented as mean ± SEM; n = 5–6.