Physiological levels of fluid shear stress modulate vascular function through TRPV4 sparklets  

作　　者：Li Geng Chi Zhang Chao He Ka Zhang Hao Kan Aiqin Mao Xin Ma 

机构地区：[1]Wuxi School of Medicine,Jiangnan University,Wuxi 214122,China [2]Department of Emergency and Critical Care,Changzheng Hospital,Naval Medical University,Shanghai 200003,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第9期1268-1277,共10页生物化学与生物物理学报（英文版）

基　　金：the grants from the National Natural Science Foundation of China(Nos.82025005,82100416,and 91939301);the Chang Jiang Scholars Program(No.Q2015106);the Shanghai Science Development Funds(No.21Y11902500).

摘　　要：Endothelial calcium(Ca^(2+))signaling plays a major role in regulating vasodilation in response to fluid shear stress(FsS)generated by blood flow.Local Ca^(2+)influx through single transient receptor potential channel subfamily V member4(TRPV4)(termed"sparklets")activated bylowconcentrations of chemical andbiological 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 theactivity of TPRV4 sparklets inducedbyvarious physiological levels of FSS and investigate the mechanisms involving these Ca?+signals in FsS-induced vasodilation.Intact small mesenteric arteries are used for Ca^(2+)imaging with a GCaMP2(TRPV4-KO)mouse model and high-speed confocal systems.Markedly increased local Ca^(2+)signals are observed in the endothelium under 4-8 dyne/cm^(2)FsS,whereas FSS>8 dyne/cm^(2)causes global Ca^(2+)influx.Further analysis shows that TRPV4 channels form a four-channel group to mediate Ca^(2+)sparklets under certain levels of Fss.The large Ca^(2+)influx hyperpolarizes endothelial cells by stimulating intermediate(IK)-and small(SK)-conductance Ca^(2+)-sensitive potassium channels,leading to hyperpolarization of the surrounding smooth muscle cells and ultimately causing endothelium-dependent vasodilation.In conclusion,Ca^(2+)influx transits through a small number of endothelial TRPV4 channels opened by certain levels of FsS,which activates the Ca^(2+)-sensitive IK and SK channels to cause vasodilation.

关 键 词：calcium sparklet ENDOTHELIUM TRPV4 shear stress VASODILATION 

分 类 号：R36[医药卫生—病理学]