TRPC3 mediates pyrimidine receptor-induced depolarization of cerebral arteries

被引:128
作者
Reading, SA [1 ]
Earley, S [1 ]
Waldron, BJ [1 ]
Welsh, DG [1 ]
Brayden, JE [1 ]
机构
[1] Univ Vermont, Dept Pharmacol, Burlington, VT 05405 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2005年 / 288卷 / 05期
关键词
transient receptor potential; nonselective cation channels; vascular smooth muscle; uridine triphosphate; vasoconstriction; antisense oligodeoxynucleotides;
D O I
10.1152/ajpheart.00861.2004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We tested the hypothesis that TRPC3, a member of the canonical transient receptor potential (TRP) family of channels, mediates agonist-induced depolarization of arterial smooth muscle cells (SMCs). In support of this hypothesis, we observed that suppression of arterial SMC TRPC3 expression with antisense oligodeoxynucleotides significantly decreased the depolarization and constriction of intact cerebral arteries in response to UTP. In contrast, depolarization and contraction of SMCs induced by increased intravascular pressure, i.e., myogenic responses, were not altered by TRPC3 suppression. Interestingly, UTP-evoked responses were not affected by suppression of a related TRP channel, TRPC6, which was previously found to be involved in myogenic depolarization and vasoconstriction. In patch-clamp experiments, UTP activated a whole cell current that was greatly reduced or absent in TRPC3 antisense-treated SMCs. These results indicate that TRPC3 mediates UTP-induced depolarization of arterial SMCs and that TRPC3 and TRPC6 may be differentially regulated by receptor activation and mechanical stimulation, respectively.
引用
收藏
页码:H2055 / H2061
页数:7
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