5 years ago

Beta-adrenergic regulation of the heart expressing the Ser1700A/Thr1704A mutated Cav1.2 channel

Beta-adrenergic stimulation of the heart increases I Ca . PKA dependent phosphorylation of several amino acids (among them Ser 1700 and Thr 1704 in the carboxy-terminus of the Cav1.2 α1c subunit) has been implicated as decisive for the β-adrenergic up-regulation of cardiac I Ca . Mutation of Ser 1700 and Thr 1704 to alanine results in the Cav1.2PKA_P2−/− mice. Cav1.2PKA_P2−/− mice display reduced cardiac L-type current. Fractional shortening and ejection fraction in the intact animal and I Ca in isolated cardiomyocytes (CM) are stimulated by isoproterenol. Cardiac specific expression of the mutated Cav1.2PKA_P2−/− gene reduces Cav1.2 α1c protein concentration, I Ca , and the β-adrenergic stimulation of L-type I Ca in CMs. Single channels were not detected on the CM surface of the cCav1.2PKA_P2−/− hearts. This outcome supports the notion that S1700/1704 is essential for expression of the Cav1.2 channel and that isoproterenol stimulates I Ca in Cav1.2PKA_P2−/− CMs.

Publisher URL: www.sciencedirect.com/science

DOI: S0022282817302730

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