Norepinephrine-induced intracellular Ca²⁺ increase is coupled with astrocytic BK channel activation and capillary response

Astrocytes are abundant glial cells organized in a meshwork in which each cell is in contact with both neuronal and vascular elements. They receive and respond to neuronal signals and modulate synaptic activity and diameter of blood vessels through changes in their intracellular Ca 2+ . Norepinephrine plays an important role in both of these astrocytic functions, however, it remains unclear whether norepinephrine-induced intracellular Ca 2+ increase leads to further cellular adjustments in astrocyte activity. Here, we reveal a causal relationship between norepinephrine-induced intracellular Ca 2+ increase, α1-adrenergic receptor activation and activation of large-conductance Ca 2+ -dependent potassium ion (BK) channel in cultured rat cortical astrocytes. BK channel activation was abolished by α1-adrenergic receptor blockade, depletion of intracellular Ca 2+ stores, or dialysis of astrocytes with a Ca 2+ chelator. We further show that this norepinephrine-induced astrocytic Ca 2+ –BK channel coupling contributes to a reduction in cortical capillary diameter. The capillary response was prevented by pharmacological silencing of astrocytes or BK channel blockade, while the norepinephrine effect was mimicked by direct BK channel activation with an agonist in acute brain slices. In summary, these results elucidate a previously unrecognized cellular response of astrocytes to norepinephrine that is coupled with modulation of capillary diameter and may represent an integral part of the astrocytic communication with neurons and blood vessels.