cAMP-dependent phosphorylation sites and macroscopic activity of recombinant cardiac L-type calcium channels |
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Authors: | Mikala Gabor Klöckners Udo Varadi Maria Eisfeld Jörg Schwartz Arnold Varadi Gyula |
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Affiliation: | (1) Institute of Molecular Pharmacology and Biophysics, University of Cincinnati, College of Medicine, 231 Bethesda Avenue, Cincinnati, OH 45267-0828, USA;(2) Department of Physiology, University of Cologne, Robert-Kochstrasse 39, 50931 Cologne, Germany |
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Abstract: | The involvement of cAMP-dependent phosphorylation sites in establishing the basal activity of cardiac L-type Ca2+ channels was studied in HEK 293 cells transiently cotransfected with mutants of the human cardiac 1 and accessory subunits. Systematic individual or combined elimination of high consensus protein kinase A (PKA) sites, by serine to alanine substitutions at the amino and carboxyl termini of the 1 subunit, resulted in Ca2+ channel currents indistinguishable from those of wild type channels. Dihydropyridine (DHP)-binding characteristics were also unaltered. To explore the possible involvement of nonconsensus sites, deletion mutants were used. Carboxyl-terminal truncations of the 1 subunit distal to residue 1597 resulted in increased channel expression and current amplitudes. Modulation of PKA activity in cells transfected with the wild type channel or any of the mutants did not alter Ca2+ channel functions suggesting that cardiac Ca2+ channels expressed in these cells behave, in terms of lack of PKA control, like Ca2+ channels of smooth muscle cells. |
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Keywords: | calcium channel phosphorylation electrophysiology mutagenesis dihydropyridine phrase |
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