FIGURE 9.

Topology of inositol trisphosphate (IP₃) receptors (IP₃Rs) and models of IP₃R interactions with other ion channels. A: structure of an IP₃R subunit. SR, sarcoplasmic reticulum. B: model. IP₃ (1) promotes (2) a physical interaction between IP₃Rs and canonical transient receptor potential (TRP) (TPRC)3 channels that (3) activates TRPC3 and promotes membrane depolarization, resulting in (4) an increase in the open probability of Ca_V1.2 channels, an elevation in intracellular Ca²⁺, and contraction of vascular smooth muscle cells. C: stretch promotes IP₃ production and activation of IP₃Rs, as well as diacylglycerol (DAG) production leading to activation of TRPC6 channels. The activation of IP₃Rs and TRPC6 channels increases local intracellular Ca²⁺ near melastatin TRP (TRPM)4 channels, which are then activated to cause membrane depolarization and vascular smooth muscle contraction. In this model, it is proposed that IP₃Rs, TPRC6, and TRPM4 form a nanocomplex. Figures created with Biorender.com.