Bestrophin-3 associated Ca²⁺-activated Cl^- conductance is important for synchronization in the arterial wall

TY - ABST

T1 - Bestrophin-3 associated Ca2+-activated Cl- conductance is important for synchronization in the arterial wall

AU - Brøgger, Torbjørn

AU - Aalkjær, Christian

AU - Matchkov, Vladimir

N1 - Conference code: 14

PY - 2009

Y1 - 2009

N2 - The cGMP-dependent Ca2+-activated Cl- current (IcGMP,Ca-Cl) has been previously suggested to be important for synchronization of smooth muscle cells (SMCs) in the vascular wall (Peng et al., Circ Res, 2001). We have characterized this current and we have shown its association with a member of bestrophin proteins family - Best-3. We have aimed here to explore the importance of Best-3 for vascular wall function.  Segments of the mesenteric small arteries were transfected in vivo in anaesthetized rats with siRNA against Best-3 and siRNA with mismatching nucleotides (mutated siRNA) as a control. The efficiency of transfection at molecular level was evaluated 3 days after transfection. Contractility, vasomotion and [Ca2+]i dynamic were tested in isometric myograph and using confocal microscope. The specific Best-3 siRNA significantly reduced Best-3 expression in comparison to the control. Arteries from different groups were similar morphologically and no difference in contractility was seen. The arteries downregulated for Best-3 had significantly reduced amplitude of vasomotion without changes in the frequency. Endothelium denudation abolished vasomotion in both groups. Addition of 8Br-cGMP to the endothelium-denuded vessels restored vasomotion but did not change the difference between groups. SMCs in control endothelium-intact arteries were completely synchronized whereas in the siRNA-transfected arteries only partial synchronization was observed. Our data suggest that the Best-3-associated IcGMP,Ca-Cl is important for the synchronization of SMCs and the generation of vasomotion.

AB - The cGMP-dependent Ca2+-activated Cl- current (IcGMP,Ca-Cl) has been previously suggested to be important for synchronization of smooth muscle cells (SMCs) in the vascular wall (Peng et al., Circ Res, 2001). We have characterized this current and we have shown its association with a member of bestrophin proteins family - Best-3. We have aimed here to explore the importance of Best-3 for vascular wall function.  Segments of the mesenteric small arteries were transfected in vivo in anaesthetized rats with siRNA against Best-3 and siRNA with mismatching nucleotides (mutated siRNA) as a control. The efficiency of transfection at molecular level was evaluated 3 days after transfection. Contractility, vasomotion and [Ca2+]i dynamic were tested in isometric myograph and using confocal microscope. The specific Best-3 siRNA significantly reduced Best-3 expression in comparison to the control. Arteries from different groups were similar morphologically and no difference in contractility was seen. The arteries downregulated for Best-3 had significantly reduced amplitude of vasomotion without changes in the frequency. Endothelium denudation abolished vasomotion in both groups. Addition of 8Br-cGMP to the endothelium-denuded vessels restored vasomotion but did not change the difference between groups. SMCs in control endothelium-intact arteries were completely synchronized whereas in the siRNA-transfected arteries only partial synchronization was observed. Our data suggest that the Best-3-associated IcGMP,Ca-Cl is important for the synchronization of SMCs and the generation of vasomotion.

M3 - Conference abstract in journal

SN - 0194-911X

JO - Hypertension

JF - Hypertension

T2 - European Council for Cardiovascular Research (ECCR)

Y2 - 9 October 2009 through 11 October 2009

ER -