Title: Moderate calcium channel dysfunction in adult mice with inducible cardiomyocyte-specific excision of the CACNB2 gene
Authors: Meissner, Marcel ×
Weissgerber, Petra
Camacho Londono, Juan E
Prenen, Jean
Link, Sabine
Ruppenthal, Sandra
Molkentin, Jeffery D
Lipp, Peter
Nilius, Bernd
Freichel, Marc
Flockerzi, Veit #
Issue Date: Feb-2011
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry
Abstract: The major L-type voltage-gated calcium channels in heart consist of an α1C (Cav1.2) subunit usually associated with an auxiliary β subunit (Cavβ2). In embryonic cardiomyocytes, both the complete and cardiac myocyte-specific null mutant of Cavβ2 resulted in reduction of L-type calcium currents by up to 75%, compromising heart function and causing defective remodelling of intra- and extra-embryonic blood vessels followed by embryonic death. Here we conditionally excised the Cavβ2 gene (cacnb2) specifically in cardiac myocytes of adult mice (KO). Upon gene deletion Cavβ2 protein expression declined by >96% in isolated cardiac myocytes and by >74% in protein fractions from heart. These latter protein fractions include Cavβ2 proteins expressed in cardiac fibroblasts. Surprisingly, mice did not show any obvious impairment although cacnb2 excision was not compensated by expression of other Cavβ proteins or changes of Cav1.2 protein levels. Calcium currents were still dihydropyridine-sensitive but current density at 0 mV was reduced by <29%. The voltage for half-maximal activation was slightly shifted to more depolarized potentials in KO cardiomyocytes compared to control cells but the difference was not significant. In summary, Cavβ2 appears to be a much stronger modulator of L-type calcium currents in embryonic than in adult cardiomyocytes. Although essential for embryonic survival, Cavβ2 down regulation in cardiomyocytes is well tolerated by the adult mice.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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