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. Author manuscript; available in PMC: 2023 May 14.
Published in final edited form as: Nat Cardiovasc Res. 2022 Nov 14;1(11):1022–1038. doi: 10.1038/s44161-022-00157-y

Fig. 1 |. Adrenergic agonist-induced stimulation of Ca2+ current requires phosphorylation of Rad in ventricular and atrial cardiomyocytes.

Fig. 1 |

a,b, Exemplar current–voltage relationships of Ca2+ channels from WT and 4SA-Rad cardiomyocytes in the absence (black trace) and presence (blue trace) of isoproterenol (ISO). Inset: exemplar whole-cell CaV1.2 currents. Pulses from −60 mV to +50 mV before (black traces) and 3 min after (blue traces) 200 nM isoproterenol. c, Ba2+ current elicited by voltage ramp from −60 mV to +30 mV, with black traces obtained before and blue traces after isoproterenol in WT and 4SA-Rad ventricular myocytes. d, Graph of maximal conductance density (at +10 mV) for WT (172 cells, 22 mice) and 4SA-Rad cardiomyocytes (56 cells, 11 mice), acquired via the step protocol. Data are the mean ± s.e.m. ***P < 0.001 by unpaired, two-tailed Student’s t-test. Specific P values can be found in the associated Source data (see Supplementary Information). e, Fold-change in peak current at −20 mV caused by isoproterenol or forskolin (FSK). Data are mean ± s.e.m. ****P < 0.0001 by unpaired, two-tailed Student’s t-test. WT: isoproterenol, 30 cells, 8 mice and forskolin, 71 cells, 15 mice; 4SA-Rad: isoproterenol, 21 cells, 4 mice and forskolin, 35 cells, 7 mice. f, V50 before and after isoproterenol or forskolin. Data are the mean ± s.e.m. ****P < 0.0001 for WT, P = 0.67 (isoproterenol), P = 0.41 (forskolin) for 4SA-Rad by unpaired, two-tailed Student’s t-test. NS, not significant. WT: isoproterenol, 30 cells, 8 mice and forskolin, 76 cells, 15 mice; 4SA-Rad: isoproterenol, 20 cells, 4 mice and forskolin, 36 cells, 7 mice. g, Same as c except with atrial cardiomyocytes. h, Diary plot of normalized fold-change of conductance at −20 mV for WT and 4SA-Rad atrial and ventricular myocytes. Data are mean ± s.e.m. Ventricle WT: 22 cells, 3 mice; 4SA-Rad: 31 cells, 3 mice; atrial WT: 29 cells, 3 mice; 4SA-Rad: 20 cells, 3 mice. i, Graph of ratio of Ba2+ conductance after to Ba2+ conductance before isoproterenol treatment versus voltage. Data are mean ± s.e.m. Ventricle WT: 29 cells, 3 mice; 4SA-Rad: 35 cells, 3 mice; atrial WT: 34 cells, 3 mice; 4SA-Rad: 29 cells, 3 mice.