First Author | Meissner M | Year | 2011 |
Journal | J Biol Chem | Volume | 286 |
Issue | 18 | Pages | 15875-82 |
PubMed ID | 21357697 | Mgi Jnum | J:172090 |
Mgi Id | MGI:5003411 | Doi | 10.1074/jbc.M111.227819 |
Citation | Meissner M, et al. (2011) Moderate Calcium Channel Dysfunction in Adult Mice with Inducible Cardiomyocyte-specific Excision of the cacnb2 Gene. J Biol Chem 286(18):15875-82 |
abstractText | The major L-type voltage-gated calcium channels in heart consist of an alpha1C (Ca(V)1.2) subunit usually associated with an auxiliary beta subunit (Ca(V)beta2). In embryonic cardiomyocytes, both the complete and the cardiac myocyte-specific null mutant of Ca(V)beta2 resulted in reduction of L-type calcium currents by up to 75%, compromising heart function and causing defective remodeling of intra- and extra-embryonic blood vessels followed by embryonic death. Here we conditionally excised the Ca(V)beta2 gene (cacnb2) specifically in cardiac myocytes of adult mice (KO). Upon gene deletion, Ca(V)beta2 protein expression declined by >96% in isolated cardiac myocytes and by >74% in protein fractions from heart. These latter protein fractions include Ca(V)beta2 proteins expressed in cardiac fibroblasts. Surprisingly, mice did not show any obvious impairment, although cacnb2 excision was not compensated by expression of other Ca(V)beta proteins or changes of Ca(V)1.2 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 when compared with control cells, but the difference was not significant. In summary, Ca(V)beta2 appears to be a much stronger modulator of L-type calcium currents in embryonic than in adult cardiomyocytes. Although essential for embryonic survival, Ca(V)beta2 down-regulation in cardiomyocytes is well tolerated by the adult mice. |