Journal
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
Volume 54, Issue 9, Pages 1268-1277Publisher
SCIENCE PRESS
DOI: 10.3724/abbs.2022118
Keywords
calcium sparklet; endothelium; TRPV4; shear stress; vasodilation
Categories
Funding
- National Natural Science Foundation of China [82025005, 82100416, 91939301]
- Chang Jiang Scholars Program [Q2015106]
- Shanghai Science Development Funds [21Y11902500]
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Endothelial calcium signaling, regulated by fluid shear stress (FSS), plays a significant role in vasodilation. TRPV4 channels mediate calcium influx in response to certain levels of FSS, leading to endothelial cell hyperpolarization and subsequent vasodilation.
Endothelial calcium (Ca2+) signaling plays a major role in regulating vasodilation in response to fluid shear stress (FSS) generated by blood flow. Local Ca2+ influx through single transient receptor potential channel subfamily V member 4 (TRPV4) (termed sparklets) activated by low concentrations of chemical and biological stimuli has been revealed to modulate vascular function. However, the range in which FSS can initiate TRPV4 sparklets to induce vasodilation is unknown. Here, we assess the activity of TPRV4 sparklets induced by various physiological levels of FSS and investigate the mechanisms involving these Ca2+ signals in FSS-induced vasodilation. Intact small mesenteric arteries are used for Cav imaging with a GCaMP2(TRPV4-KO) mouse model and high-speed confocal systems. Markedly increased local Ca2+ signals are observed in the endothelium under 4-8 dyne/cm(2) FSS, whereas FSS > 8 dyne/cm(2) causes global Ca2+ influx. Further analysis shows that TRPV4 channels form a four-channel group to mediate Ca2+ sparklets under certain levels of FSS. The large Ca2+ influx hyperpolarizes endothelial cells by stimulating intermediate (IK)- and small (SK)-conductance Ca2+-sensitive potassium channels, leading to hyperpolarization of the surrounding smooth muscle cells and ultimately causing endothelium-dependent vasodilation. In conclusion, Ca2+ influx transits through a small number of endothelial TRPV4 channels opened by certain levels of FSS, which activates the Ca2+-sensitive IK and SK channels to cause vasodilation.
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