UC Irvine

The range of action of intracellular messengers is determined by their rates of diffusion and degradation. Previous measurements in oocyte cytoplasmic extracts indicated that the Ca²⁺-liberating second messenger inositol trisphosphate (IP₃) diffuses with a coefficient (~280 μm² s^-1) similar to that in water, corresponding to a range of action of ~25 μm. Consequently, IP₃ is generally considered a "global" cellular messenger. We reexamined this issue by measuring local IP₃-evoked Ca²⁺ puffs to monitor IP₃ diffusing from spot photorelease in neuroblastoma cells. Fitting these data by numerical simulations yielded a diffusion coefficient (≤10 μm² s^-1) about 30-fold slower than that previously reported. We propose that diffusion of IP₃ in mammalian cells is hindered by binding to immobile, functionally inactive receptors that were diluted in oocyte extracts. The predicted range of action of IP₃ (<5 μm) is thus smaller than the size of typical mammalian cells, indicating that IP₃ should better be considered as a local rather than a global cellular messenger.