TRPC1 associates with BKCa channel to form a signal complex in vascular smooth muscle cells

Hiu Yee Kwan, Bing Shen, Xin Ma, Yuk Chi Kwok, Yu Huang, Yu Bun Man, Shan Yu, Xiaoqiang Yao*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

100 Citations (Scopus)

Abstract

TRPC1 (transient receptor potential canonical 1) is a Ca 2+-permeable cation channel involved in diverse physiological function. TRPC1 may associate with other proteins to form a signaling complex, which is crucial for channel function. In the present study, we investigated the interaction between TRPC1 and large conductance Ca2+-sensitive K+ channel (BKCa). With the use of potentiometric fluorescence dye DiBAC4(3), we found that store-operated Ca 2+ influx resulted in membrane hyperpolarization of vascular smooth muscle cells (VSMCs). The hyperpolarization was inhibited by an anti-TRPC1 blocking antibody T1E3 and 2 BKCa channel blockers, charybdotoxin and iberiotoxin. These data were confirmed by sharp microelectrode measurement of membrane potential in VSMCs of intact arteries. Furthermore, T1E3 treatment markedly enhanced the membrane depolarization and contraction of VSMCs in response to several contractile agonists including phenylephrine, endothelin-1, and U-46619. In coimmunoprecipitation experiments, an antibody against BK Ca α-subunit [BKCa(α)] could pull down TRPC1, and moreover an anti-TRPC1 antibody could reciprocally pull down BK Ca(α). Double-labeling immunocytochemistry showed that TRPC1 and BKCa were colocalized in the same subcellular regions, mainly on the plasma membrane, in VSMCs. These data suggest that, TRPC1 physically associates with BKCa in VSMCs and that Ca influx through TRPC1 activates BKCa to induce membrane hyperpolarization. The hyperpolarizing effect of TRPC1-BKCa coupling could serve to reduce agonist-induced membrane depolarization, thereby preventing excessive contraction of VSMCs to contractile agonists.

Original languageEnglish
Pages (from-to)670-678
Number of pages9
JournalCirculation Research
Volume104
Issue number5
DOIs
Publication statusPublished - 13 Mar 2009

Scopus Subject Areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

User-Defined Keywords

  • BKca
  • Hyperpolarization
  • Physical coupling
  • TRPC1
  • Vascular smooth muscle cells

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