Local IP3 receptor-mediated Ca2+ signals compound to direct blood flow in brain capillaries

Healthy brain function depends on the finely tuned spatial and temporal delivery of blood-borne nutrients to active neurons via the vast, dense capillary network. Here, using in vivo imaging in anesthetized mice, we reveal that brain capillary endothelial cells control blood flow through a hierarchy of IP3 receptor-mediated Ca2+ events, ranging from small, subsecond protoevents, reflecting Ca2+ release through a small number of channels, to high-amplitude, sustained (up to similar to 1 min) compound events mediated by large clusters of channels. These frequent (similar to 5000 events/s per microliter of cortex) Ca2+ signals are driven by neuronal activity, which engages G(q) protein-coupled receptor signaling, and are enhanced by Ca2+ entry through TRPV4 channels. The resulting Ca2+-dependent synthesis of nitric oxide increases local blood flow selectively through affected capillary branches, providing a mechanism for high-resolution control of blood flow to small clusters of neurons.

Automated summary

The study reveals that brain capillary endothelial cells control blood flow through a series of Ca2+ events, driven by neuronal activity and Ca2+ entry through TRPV4 channels. This provides a mechanism for high-resolution control of blood flow to small clusters of neurons.