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Göteborgs universitets publikationer

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

Författare och institution:
Vladimir V Matchkov (-); Per Larsen (-); Elena V Bouzinova (-); Aleksandra Rojek (-); Donna M Briggs Boedtkjer (-); Veronika Golubinskaya (-); Finn Skou Pedersen (-); Christian Aalkjaer (-); Holger Nilsson (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi)
Publicerad i:
Circulation research, 103 ( 8 ) s. 864-72
Artikel, refereegranskad vetenskaplig
Sammanfattning (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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Animals, Aorta, metabolism, Calcium, metabolism, Cells, Cultured, Chloride Channels, genetics, metabolism, Chlorides, metabolism, Cyclic GMP, metabolism, Male, Membrane Potentials, Mesenteric Arteries, metabolism, Muscle Proteins, genetics, metabolism, Muscle, Smooth, Vascular, drug effects, metabolism, Myocytes, Smooth Muscle, drug effects, metabolism, Niflumic Acid, pharmacology, Pulmonary Artery, metabolism, RNA Interference, RNA, Messenger, metabolism, RNA, Small Interfering, metabolism, Rats, Rats, Wistar, Transfection
Postens nummer:
Posten skapad:
2008-12-02 13:12
Posten ändrad:
2009-10-02 12:14

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