Abstract 409: LRRC10 Associates With and Regulates Cardiac CaV1.2 L-type Ca2+ Channels, and I195T LRRC10 Variant is Linked to Dilated Cardiomyopathy

Leucine-rich repeat containing (LRR) proteins facilitate protein-protein interactions critical in a number of cellular functions including ion channel regulation. Leucine-rich repeat containing protein 10 (LRRC10), a cardiac-specific protein expressed in zebrafish, mice and humans, is essential for normal cardiac physiology with loss of Lrrc10 in Lrrc10-/- mice resulting in dilated cardiomyopathy (DCM). However, the mechanism by which LRRC10 contributes to DCM is unknown. Further, the functional role of LRRC10 in the regulation of ion channels in the heart has not been explored. Here we recorded L-type Ca2+ channel currents (ICa,L) from isolated ventricular myocytes of WT and Lrrc10-/- mice, demonstrating a significant reduction in ICa,L in Lrrc10-/- myocytes (-4.9 ± 0.19 pA/pF, n=10) compared to WT (-6.5 ± 0.24 pA/pF, n=8). Co-immunoprecipitation (co-IP) experiments showed an association between LRRC10 and Cav1.2 in WT, but not Lrrc10-/- mouse lysates, with immunocytochemistry studies further demonstrati...