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Mice with cardiac-specific sequestration of the β-subunit of the L-type calcium channel

Item Type:Article
Title:Mice with cardiac-specific sequestration of the β-subunit of the L-type calcium channel
Creators Name:Serikov, V. and Bodi, I. and Koch, S.E. and Muth, J.N. and Mikala, G. and Martinov, S.G. and Haase, H. and Schwartz, A.
Abstract:The {beta} subunit of the L-type voltage-dependent calcium channel modifies the properties of the channel complex by both allosteric modulation of the {alpha}1 subunit function and by chaperoning the translocation of the {alpha}1 subunit to the plasma membrane. The goal of this study was to investigate the functional effect of changing the in vivo stoichiometry between the {alpha}1 and {beta} subunits by creating a dominant negative expression system in a transgenic mouse model. The high affinity {beta} subunit-binding domain of the {alpha}1 subunit was overexpressed in a cardiac-specific manner to act as a {beta} subunit trap. We found that the predominant {beta} isoform was located primarily in the membrane bound fraction of heart protein, whereas the {beta}1 and {beta}3 were mostly cytosolic. There was a significant diminution of the amount of {beta}2 in the membrane fraction of the transgenic animals, resulting in a decrease in contractility of the heart and a decrease in L-type calcium current density in the myocyte. However, there were no distinguishable differences in {beta}1 and {beta}3 protein expression levels in the membrane bound fraction between transgenic and non-transgenic animals. Since the {beta}1 and {beta}3 isoforms only make up a small portion of the total {beta} subunit in the heart, slight changes in this fraction are not detectable using Western analysis. In contrast, {beta}1 and {beta} in skeletal muscle and brain, the predominant isoforms in these tissues, respectively, are membrane bound.
Keywords:Sequestration of {beta} Subunit in Mouse Heart, Animals, Mice
Source:Biochemical and Biophysical Research Communications
Publisher:Academic Press (U.S.A.)
Page Range:1405-1411
Date:24 May 2002
Official Publication:https://doi.org/10.1016/S0006-291X(02)00396-0
PubMed:View item in PubMed

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