Abstract 20669: LRRC10 and Dilated Cardiomyopathy-Associated I195T LRRC10 Mutation Differentially Regulate Cav1.2 L-Type Ca2+ Channels

Leucine-rich repeat containing protein 10 (LRRC10) is a cardiac-specific protein and loss of LRRC10 in LRRC10-/- mice results in dilated cardiomyopathy (DCM). Here we describe a novel mutation in human LRRC10, I195T, associated with early onset DCM. However, the mechanism by which LRRC10 and mutations in LRRC10 contribute to DCM remains unknown. Because LRRC10-/- hearts exhibit defective contractility and LRRC10 is localized to the dyad, we tested the hypothesis that LRRC10 interacts with and regulates Cav1.2 channels. We performed whole-cell patch clamp electrophysiology on isolated ventricular myocytes from wild-type (WT) and LRRC10-/- mice. The L-type Ca2+ currents (ICa,L) was significantly decreased in LRRC10-/- myocytes (-4.9 ± 0.22 pA/pF, N=10; 7 mice) compared to wild-type (-7.7 ± 0.72 pA/pF, N=5; 4 mice). The voltage dependence of current activation and inactivation, however, were not significantly different between LRRC10-/- and WT. Western blot experiments using heart lysates from LRRC10-/- and ...