• Patchliner

    兼顾科研与工业的全自动膜片钳系统
  • Patchliner

    自主生产与质量控制的耗材
  • Patchliner

    拥有超过10年实验设计与支持的经验
  • Dynamite8

    Automated Dynamic Clamp
  • Patchliner

    拥有所有手动膜片钳的特征与优点

2010 - Pregnenolone Sulphate- and Cholesterol-Regulated TRPM3 Channels Coupled to Vascular Smooth Muscle Secretion and Contraction

icon pl  Patchliner publication in Circulation Research (2010)

Authors: 
Naylor J., Li J., Milligan C.J, Zeng F., Sukumar P., Hou B., Sedo A., Yuldasheva N., Majeed Y., Beri D., Jiang S., Seymour V.A.L, McKeown L., Kumar B., Harteneck C., O'Regan D., Wheatcroft S.B., Kearney M.T, Jones C., Porter K.E., Beech D.J.

 

Journal: 
Circ. Res. (2010)


Abstract: 

Rationale:
Transient receptor potential melastatin (TRPM)3 is a calcium-permeable ion channel activated by the neurosteroid pregnenolone sulfate and positively coupled to insulin secretion in β cells. Although vascular TRPM3 mRNA has been reported, there is no knowledge of TRPM3 protein or its regulation and function in the cardiovascular system.

Objective:
To determine the relevance and regulation of TRPM3 in vascular biology.

Methods and Results:
TRPM3 expression was detected at mRNA and protein levels in contractile and proliferating vascular smooth muscle cells. Calcium entry evoked by pregnenolone sulfate or sphingosine was suppressed by TRPM3 blocking antibody or knock-down of TRPM3 by RNA interference. Low-level constitutive TRPM3 activity was also detected. In proliferating cells, channel activity was coupled negatively to interleukin-6 secretion via a calcium-dependent mechanism. In freshly isolated aorta, TRPM3 positively modulated contractile responses independently of L-type calcium channels. Concentrations of pregnenolone sulfate required to evoke responses were higher than the known plasma concentrations of the steroids, leading to a screen for other stimulators. β-Cyclodextrin was one of few stimulators of TRPM3, revealing the channels to be partially suppressed by endogenous cholesterol, the precursor of pregnenolone. Elevation of cholesterol further suppressed channel activity and loading with cholesterol to generate foam cells precluded observation of TRPM3 activity.

Conclusions:
The data suggest functional relevance of TRPM3 in contractile and proliferating phenotypes of vascular smooth muscle cells, significance of constitutive channel activity, regulation by cholesterol, and potential value of pregnenolone sulfate in therapeutic vascular modulation.


Download here

返回总览

We use cookies on our website. Some of them are essential for the operation of the site, while others help us to improve this site and the user experience (tracking cookies). You can decide for yourself whether you want to allow cookies or not. Please note that if you reject them, you may not be able to use all the functionalities of the site.