Endothelial TRPV4 channels modulate vascular tone by Ca2+‐induced Ca2+ release at inositol 1,4,5‐trisphosphate receptors

• DOI: 10.1111/bph.14762
• Publication Date: 2019-06-09T06:25:12Z
• Authors: Helen R. Heathcote; Matthew D. Lee; Xun Zhang; Christopher D. Sa...; Calum Wilson; John G. McCarron
• Keywords: Vascular tone; Inositol trisphosphate receptor

The TRPV4 ion channels are Ca2+ permeable, non-selective cation that mediate large, but highly localized, signals in the endothelium. mechanisms permit localized changes to evoke cell-wide activity incompletely understood. Here, we tested hypothesis TRPV4-mediated influx activates release from internal stores generate widespread effects.Ca2+ large numbers (~100) of endothelial cells intact arteries were imaged and analysed separately.Responses channel agonist GSK1016790A heterogeneous across In activated cells, responses comprised leading slow, persistent, global increases followed by propagating waves moved within between cells. To examine underlying each component, developed methods separate slow persistent rise cell. entry was required for signals. inhibited depleting stores, inhibiting PLC or blocking IP3 receptors. tightly controlled ceased when terminated. Furthermore, essential control vascular tone.Ca2+ via is amplified -induced acting at receptors provide a large-scale communication system. tone requires store.