Ser(1901) of alpha(1C) subunit is required for the PKA-mediated enhancement of L-type Ca(2+) channel currents but not for the negative shift of activation.
Cardiac L-type Ca(2+) channel is facilitated by protein kinase A (PKA)-mediated phosphorylation. Here, we investigated the role of Ser(1901), a putative phosphorylation site in the carboxy-terminal of rat brain type-II alpha(1C) subunit (rbCII), in the PKA-mediated regulation. Forskolin (3 microM) enhanced Ca(2+) channel currents (I(Ca)) and shifted the activation curve to negative voltages, which were abolished by protein kinase inhibitor. Replacement of Ser(1901) of rbCII by Ala abolished the enhancement of I(Ca) by forskolin but not the shift of the activation curve. These results indicate that Ser(1901) is required for the PKA-mediated enhancement of I(Ca), and that the voltage-dependence of the activation of I(Ca) appears to be modulated via another PKA phosphorylation site.
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
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Naguro
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Nagao
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Adachi-Akahane
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D006224:Cricetinae; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D020746:Calcium Channels, L-Type; D012694:Serine; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases