Circ Res. 2009 Mar 13;104(5):670-8. doi: 10.1161/CIRCRESAHA.108.188748. Epub 2009 Jan 22.

TRPC1 associates with BK(Ca) channel to form a signal complex in vascular smooth muscle cells.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

Kwan, H. Y., Shen, B., Ma, X., Kwok, Y. C., Huang, Y., Man, Y. B., Yu, S., Yao, X.,
["Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, and Department of Physiology, The Chinese University of Hong Kong, Hong Kong, China."]
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 Ca(2+)-sensitive K(+) channel (BK(Ca)). With the use of potentiometric fluorescence dye DiBAC(4)(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 BK(Ca) 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) alpha-subunit [BK(Ca)(alpha)] could pull down TRPC1, and moreover an anti-TRPC1 antibody could reciprocally pull down BK(Ca)(alpha). Double-labeling immunocytochemistry showed that TRPC1 and BK(Ca) were colocalized in the same subcellular regions, mainly on the plasma membrane, in VSMCs. These data suggest that, TRPC1 physically associates with BK(Ca) in VSMCs and that Ca(2+) influx through TRPC1 activates BK(Ca) to induce membrane hyperpolarization. The hyperpolarizing effect of TRPC1-BK(Ca) coupling could serve to reduce agonist-induced membrane depolarization, thereby preventing excessive contraction of VSMCs to contractile agonists.
PMID: 19168436External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BKca Inference Prediction 19168436
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Assay with endogenous proteins Assay with overexpressed proteins Reference
Cell or tissue Cell or tissue TRP channel construct Interactor construct
TRP channel Interactor Method Species Region Species Region
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BKca Co-immunofluorescence staining Rat aortic vascular smooth muscle cell 19168436
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BKca Co-immunoprecipitation HEK293 Human Full-length Human Full-length 19168436
TRPC1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BKca Co-immunoprecipitation Rat vascular smooth muscle cell 19168436
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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