Ca²⁺Channel Control of Calcium-activated Chloride Channel Function in Brain Thin-strand Pericytes

Thin-strand pericytes extend their fine processes across the deepest regions of the brain's capillary network, intimately associating with adjacent endothelial cells. As they are position in close proximity to neurons, thin-strand pericytes have been implicated in regulating blood flow via membrane potential changes mediated by electrical signaling. We have identified functional calcium (Ca 2+ )-activated Cl - channels (CaCCs), encoded by the Ano1 gene, in thin-strand pericytes using genetic and pharmacological approaches. Our findings demonstrate that CaCC activation is predominantly driven by L-type voltage-dependent Ca 2+ channels (VDCCs) and endoplasmic reticulum Ca 2+ release through IP3 receptors and ryanodine receptors. We also confirmed the functional presence of T-type VDCCs in these cells, and our data support their contribution to CaCC activation alongside L-type VDCCs. We propose that interactions between L- and T-type VDCCs and internal Ca 2+ stores together finely tune CaCC activation. These results provide insight into the physiological role of CaCCs in thin-strand pericytes and serve as a stepping stone for understanding the broader role of pericytes in regulating capillary blood flow in the brain. the Chan Zuckerberg Initiative (Project CP-2-1-Longden to T.A.L). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.