Science Signaling· 2026Q1
ORAI Ca 2+ channels and STIM1 drive capillary-to-arteriole communication in neurovascular coupling
- 1citations
- Q1SCImago
- 2026year
Short summary
ORAI1 channels and STIM1 are essential for communication from capillaries to arterioles, driving blood flow increases during sustained neuronal activity.
AI-generated from the title and abstract; the full text is not read.
Key points
- ORAI1 channels and STIM1 are essential for capillary-to-arteriole communication in neurovascular coupling.
- Endothelial cell-specific knockout of Stim1 or Orai1 impaired sustained arteriole dilation and reduced blood flow increases during neuronal stimulation.
- Deficiency in endothelial Stim1 or Orai1 led to cognitive impairment in mice.
- Deficiency in endothelial Orai3 led to anxiety-like behaviors in mice.
AI-generated from the title and abstract; the full text is not read.
Abstract
Neurovascular coupling (NVC), which is initiated by the brain’s dense capillary network, matches blood flow to neuronal activity. We found that ORAI1 channels and their regulator STIM1, the main drivers of store-operated Ca 2+ entry, were essential for communication from capillaries, which detect neuronal metabolic need, to upstream arterioles, which dilate to increase regional flow. Endothelial cell–specific knockout of either Stim1 or Orai1 disrupted capillary Ca 2+ signals, impaired sustained capillary-driven arteriole dilation, and reduced increases in blood flow in the somatosensory cortex evoked by whisker stimulation, indicating that ORAI1 and STIM1 sustain cerebral blood flow during prolonged neuronal stimulation. Moreover, mice with endothelial cell–specific deficiency of Stim1 or Orai1 showed cognitive impairment, whereas mice with endothelial cell–specific deficiency of Orai3 showed anxiety-like behaviors. These in vivo results link impaired capillary-to-arteriole signaling to isoform-specific behavioral aberrations. These findings demonstrate that intravascular communication mediated by ORAI channels and STIM1 is fundamental for NVC and brain health.
The authors' abstract, as published at the source. Science Signaling, 2026 · DOI ↗
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Field: Sensory Systems
Sensory SystemsNeuroscience