Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells.

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Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells. / Matchkov, Vladimir; Larsen, Per; Bouzinova, Elena V.; Rojek, Aleksandra; Golubinskaya, Veronika; Bødtkjer, Donna Marie Briggs; Pedersen, Finn Skou; Aalkjær, Christian; Nilsson, Holger.

I: Circulation Research, Bind 103, Nr. 8, 10.10.2008, s. 864-872.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{b33f36f0aa6b11dd889c000ea68e967b,
title = "Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells.",
abstract = "Although the biophysical fingerprints (ion selectivity, voltage-dependence, kinetics, etc) of Ca(2+)-activated Cl(-) currents are well established, their molecular identity is still controversial. Several molecular candidates have been suggested; however, none of them has been fully accepted. We have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a {"}classic{"} (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small interfering RNA both in cultured cells and in vascular smooth muscle cells in vivo was associated with a significant reduction of the cGMP-dependent Ca(2+)-activated Cl(-) current, whereas the magnitude of the classic Ca(2+)-activated Cl(-) current was not affected. The majority of previous suggestions that bestrophins are a new Cl(-) channel family were based on heterologous expression in cell culture studies. Our present results demonstrate that at least 1 family member, bestrophin-3, is essential for a well-defined endogenous Ca(2+)-activated Cl(-) current in smooth muscles in the intact vascular wall.",
author = "Vladimir Matchkov and Per Larsen and Bouzinova, {Elena V.} and Aleksandra Rojek and Veronika Golubinskaya and B{\o}dtkjer, {Donna Marie Briggs} and Pedersen, {Finn Skou} and Christian Aalkj{\ae}r and Holger Nilsson",
year = "2008",
month = oct,
day = "10",
language = "English",
volume = "103",
pages = "864--872",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "AHA/ASA",
number = "8",

}

RIS

TY - JOUR

T1 - Bestrophin-3 (vitelliform macular dystrophy 2-like 3 protein) is essential for the cGMP-dependent calcium-activated chloride conductance in vascular smooth muscle cells.

AU - Matchkov, Vladimir

AU - Larsen, Per

AU - Bouzinova, Elena V.

AU - Rojek, Aleksandra

AU - Golubinskaya, Veronika

AU - Bødtkjer, Donna Marie Briggs

AU - Pedersen, Finn Skou

AU - Aalkjær, Christian

AU - Nilsson, Holger

PY - 2008/10/10

Y1 - 2008/10/10

N2 - Although the biophysical fingerprints (ion selectivity, voltage-dependence, kinetics, etc) of Ca(2+)-activated Cl(-) currents are well established, their molecular identity is still controversial. Several molecular candidates have been suggested; however, none of them has been fully accepted. We have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a "classic" (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small interfering RNA both in cultured cells and in vascular smooth muscle cells in vivo was associated with a significant reduction of the cGMP-dependent Ca(2+)-activated Cl(-) current, whereas the magnitude of the classic Ca(2+)-activated Cl(-) current was not affected. The majority of previous suggestions that bestrophins are a new Cl(-) channel family were based on heterologous expression in cell culture studies. Our present results demonstrate that at least 1 family member, bestrophin-3, is essential for a well-defined endogenous Ca(2+)-activated Cl(-) current in smooth muscles in the intact vascular wall.

AB - Although the biophysical fingerprints (ion selectivity, voltage-dependence, kinetics, etc) of Ca(2+)-activated Cl(-) currents are well established, their molecular identity is still controversial. Several molecular candidates have been suggested; however, none of them has been fully accepted. We have recently characterized a cGMP-dependent Ca(2+)-activated Cl(-) current with unique characteristics in smooth muscle cells. This novel current has been shown to coexist with a "classic" (cGMP-independent) Ca(2+)-activated Cl(-) current and to have characteristics distinct from those previously known for Ca(2+)-activated Cl(-) currents. Here, we suggest that a bestrophin, a product of the Best gene family, is responsible for the cGMP-dependent Ca(2+)-activated Cl(-) current based on similarities between the membrane currents produced by heterologous expressions of bestrophins and the cGMP-dependent Ca(2+)-activated Cl(-) current. This is supported by similarities in the distribution pattern of the cGMP-dependent Ca(2+)-activated Cl(-) current and bestrophin-3 (the product of Best-3 gene) expression in different smooth muscle. Furthermore, downregulation of Best-3 gene expression with small interfering RNA both in cultured cells and in vascular smooth muscle cells in vivo was associated with a significant reduction of the cGMP-dependent Ca(2+)-activated Cl(-) current, whereas the magnitude of the classic Ca(2+)-activated Cl(-) current was not affected. The majority of previous suggestions that bestrophins are a new Cl(-) channel family were based on heterologous expression in cell culture studies. Our present results demonstrate that at least 1 family member, bestrophin-3, is essential for a well-defined endogenous Ca(2+)-activated Cl(-) current in smooth muscles in the intact vascular wall.

M3 - Journal article

VL - 103

SP - 864

EP - 872

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 8

ER -