Sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit in rabbits.
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.
Fowler
Mark R
MR
Faculty of Biomedical & Life Sciences, West Medical Building, University of Glasgow, Glasgow G12 8QQ, UK.
Colotti
Gianni
G
Chiancone
Emilia
E
Smith
Godfrey L
GL
Fearon
Ian M
IM
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
D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; C419385:L-type calcium channel alpha(1C); D011994:Recombinant Proteins; D001464:Barium; D002118:Calcium