E3-targeted anti-TRPC5 antibody inhibits store-operated calcium entry in freshly isolated pial arterioles

被引:75
作者
Xu, Shang-Zhong
Boulay, Guylain
Flemming, Richard
Beech, David J. [1 ]
机构
[1] Univ Leeds, Inst Membrane & Syst Biol, Leeds LS2 9JT, W Yorkshire, England
[2] Univ Sherbrooke, Dept Pharmacol, Sherbrooke, PQ J1K 2R1, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2006年 / 291卷 / 06期
基金
英国惠康基金;
关键词
arteriole; smooth muscle cell; calcium channel; store-operated channel; transient receptor potential; functional antibody;
D O I
10.1152/ajpheart.00495.2006
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Smooth muscle cells in arterioles have pivotal roles in the determination of blood pressure and distribution of local blood flow. The cells exhibit calcium entry in response to passive store depletion, but the mechanisms and relevance of this phenomenon are poorly understood. Previously, a role for canonical transient receptor potential 1 (TRPC1) was indicated, but heterologous expression studies showed TRPC1 to have poor function in isolation, suggesting a requirement for additional proteins. Here we test the hypothesis that TRPC5 is such an additional protein, because TRPC5 forms heteromultimeric channels with TRPC1, and RNA encoding TRPC5 is present in arterioles. Recordings were from arteriolar fragments freshly isolated from rabbit pial membrane. Ionic current in response to store depletion has properties like that of the TRPC1/TRPC5 heteromultimer, and so the effect of the E3-targeted, externally acting, anti-TRPC5 blocking antibody (T5E3) was explored. T5E3 suppressed calcium entry in store-depleted arterioles but had no effect in the absence of store depletion. T5E3 preadsorbed to its antigenic peptide did not inhibit calcium entry. TRPC6 is commonly detected in smooth muscle and is present in the arterioles, but T5E3 had no effect on TRPC6. The data suggest that calcium entry occurring in response to passive store depletion in smooth muscle cells of arterioles involves TRPC5 as well as TRPC1.
引用
收藏
页码:H2653 / H2659
页数:7
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