Figure 6. Activation by ADPR of nvTRPM2 current in the presence of external but absence of cytosolic Ca²⁺.

(A) Cartoon interpretation of the molecular events that occur during consecutive time intervals (sections a-g, also identified by intermittent gray shading in (A)-(B)) of the current recording in (B). Membrane, light cyan; nvTRPM2 protein, dark gray; Ca²⁺ ions, magenta spheres; ADPR, green letters ‘A’; direction of Ca²⁺ flow, yellow arrows. (B) In the presence of 1 mM external Ca²⁺, at −20 mV membrane potential, a fraction of the macroscopic nvTRPM2 current evoked by cytosolic exposure to 100 μM ADPR +125 μM free Ca²⁺ survives cytosolic Ca²⁺ removal, and subsides only upon removal of ADPR (see Figure 5E). A second application of 100 μM ADPR, without cytosolic Ca²⁺, activates a current comparable to that which survived prior Ca²⁺ removal. Note delayed current activation following exposure to ADPR alone.