title: Sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit in rabbits.
abstract: We examined the modulation of the cardiac L-type Ca(2+) channel (LTCC) by the regulatory protein sorcin and tested the hypothesis that modulation occurred by direct interaction. Whole-cell patch-clamp recordings were made on native rabbit ventricular myocytes and HEK 293 cells expressing cardiac alpha(1C) subunits. In ventricular cells, sorcin increased peak current when using either Ca(2+) or Ba(2+) as charge carriers. In HEK 293 cells, sorcin increased peak current density when using Ba(2+) as a charge carrier but not when using Ca(2+). In ventricular myocytes, current inactivation (tau(fast), in ms) was slowed by sorcin with Ca(2+) as the charge carrier, whilst in the presence of Ba(2+) it was enhanced. In HEK 293 cells, sorcin significantly enhanced tau(fast), but no significant change was observed with Ba(2+). This trend was mimicked by the truncated peptide, sorcin Ca(2+)-binding domain, which lacks the N-terminal domain. These data suggest that sorcin interacts with LTCC via its C-terminal domain, which alters current magnitude and tau(fast). These effects appear to be influenced by the prevailing experimental conditions.
authors.affiliation: Faculty of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Fowler
authors.forename: Gianni
authors.initials: G
authors.lastname: Colotti
authors.forename: Emilia
authors.initials: E
authors.lastname: Chiancone
authors.forename: Godfrey L
authors.initials: GL
authors.lastname: Smith
authors.forename: Ian M
authors.initials: IM
authors.lastname: Fearon
mesh_terms: D000818:Animals; D001464:Barium / Q000378:metabolism; D001665:Binding Sites; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; C419385:L-type calcium channel alpha(1C); D011994:Recombinant Proteins; D001464:Barium; D002118:Calcium