Fig. 1. Interaction of NCS-1 and InsP3R.
(A) Upon binding of InsP3, the InsP3R releases calcium from the ER. (B) NCS-1 alone is not sufficient to activate InsP3R. (C) Binding of NCS-1 enhances InsP3 mediated InsP3R channel activity by increasing the open probability and mean open time. (D) Lithium offsets NCS-1 mediated enhancing effects on InsP3R. (E) Paclitaxel binds the hydrophobic cleft of NCS-1 in calcium-bound state. Thereby it facilitates binding of NCS-1 to InsP3R, thus inducing calcium oscillations. (F) Lithium (as well as ibudilast) inhibit paclitaxel mediated, NCS-1 dependent increases in InsP3R channel activity, preventing calcium oscillations. Note that many NCS-1 molecules are membrane bound.