Data Supplement
Files in this Data Supplement:
- Supplemental Figures -
Supplemental Figure 1 - Chemical structure and synthesis scheme for SPM-354
Supplemental Figure 2 - Apparent affinities and slopes of SPM-354 for antagonizing Beta-arrestin recruitment by S1P in (A) S1P1 or (B) S1P3 cells, and CYM-5541-induced Beta-arrestin recruitment in S1P3 cells
Supplemental Figure 3 - Typical chronotropic responses in WT (blue) and S1P3-KO (red) mice to i.p. administration of L-adrenaline (2mg/kg), Isoproterenol/Propranolol (0.1 and 1 mpk, respectively), and Carbamylcholine/Atropine
Supplemental Figure 4 - FTY720-induced bradycardia is not sensitive to W146 reversal
Supplemental Figure 5 - Schematic representation and screening strategy of S1P3 knockin mouse, the making of the of s1p3 mCherry/mCherrymouse
Supplemental Figure 6 - S1P3 expression and function in the KI mouse
Supplemental Figure 7 - High-power confocal view of KI heart with merged S1P3 (red), HCN4, (green) and DAPI (blue) stains, and, respective, single-channel monochromatic images
Supplemental Figure 8 - Fluorescence quantification of HCN4-and S1P3-mCherry co-expression in AVN and SAN
Supplemental Figure 9 - Co-expression of mCherry fluorescence with CD31 (A and B) and Pan-neuronal markers (C) in KI mouse ventricle
Supplemental Figure 10 - S1P-induced CHB occurs irrespective of S1P-mediated CF rate reduction
Supplemental Figure 11 - Critical dependency of S1P3 on S1P-induced acute RR-interval prolongation