TRPC1 Associates With BKCa Channel to Form a Signal Complex in Vascular Smooth Muscle Cells

TRPC1 (transient receptor potential canonical 1) is a Ca2+-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 Ca2+ 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...