Sorcin modulates cardiac L-type Ca2+ current by functional interaction with the α1C subunit in rabbits

Abstract

We examined the modulation of the cardiac L-type Ca2+ 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 α1C subunits. In ventricular cells, sorcin increased peak current when using either Ca2+ or Ba2+ as charge carriers. In HEK 293 cells, sorcin increased peak current density when using Ba2+ as a charge carrier but not when using Ca2+. In ventricular myocytes, current inactivation (τfast, in ms) was slowed by sorcin with Ca2+ as the charge carrier, whilst in the presence of Ba2+ it was enhanced. In HEK 293 cells, sorcin significantly enhanced τfast, but no significant change was observed with Ba2+. This trend was mimicked by the truncated peptide, sorcin Ca2+-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 τfast. These effects appear to be influenced by the prevailing experimental conditions. © 2008 The Authors.