Ser(1901) of alpha(1C) subunit is required for the PKA-mediated enhancement of L-type Ca2+ channel currents but not for the negative shift of activation

Cardiac L-type Ca2+ channel is facilitated by protein kinase A (PKA)-mediat ed phosphorylation. Here, me investigated the role of Ser(1901), a putative phosphorylation site in the carboxy-terminal of rat brain type-II are subu nit (rbCII), in the PKA-mediated regulation, Forskolin (3 muM) enhanced Ca2 + channel currents (I-Ca) and shifted the activation curve to negative volt ages, which were abolished by protein kinase inhibitor. Replacement of Ser( 1901) of rbCII by Ala abolished the enhancement of I-Ca by forskolin but no t 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 PK A phosphorylation site. (C) 2001 Federation of European Biochemical Societi es. Published by Elsevier Science B.V. All rights reserved.