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

Vladimir Serikov, Ilona Bodi, Sheryl E. Koch, James N. Muth, Gabor Mikala, Sergey G. Martinov, Hannelore Haase, Arnold Schwartz

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The β subunit of the L-type voltage-dependent calcium channel modifies the properties of the channel complex by both allosteric modulation of the α1 subunit function and by chaperoning the translocation of the α1 subunit to the plasma membrane. The goal of this study was to investigate the functional effect of changing the in vivo stoichiometry between the α1 and β subunits by creating a dominant negative expression system in a transgenic mouse model. The high affnity β subunit-binding domain of the α1 subunit was overexpressed in a cardiac-specific manner to act as a β subunit trap. We found that the predominant β isoform was located primarily in the membrane bound fraction of heart protein, whereas the β1 and β3 were mostly cytosolic. There was a significant diminution of the amount of β2 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 β1 and β3 protein expression levels in the membrane bound fraction between transgenic and non-transgenic animals. Since the β1 and β3 isoforms only make up a small portion of the total β subunit in the heart, slight changes in this fraction are not detectable using Western analysis. In contrast, β1 and β3 in skeletal muscle and brain, the predominant isoforms in these tissues, respectively, are membrane bound.

Original languageEnglish
Pages (from-to)1405-1411
Number of pages7
JournalBiochemical and biophysical research communications
Volume293
Issue number5
DOIs
Publication statusPublished - Jan 1 2002

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Keywords

  • Sequestration of β subunit in mouse heart

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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