Figure 4. β-adrenergic regulation of GGG and 9* Ca²⁺ channels in cardiomyocytes.

(A, C, E) Current-voltage relationships before and after 10 μM forskolin in the presence of 300 nM nisoldipine. Representative of pseudo-wild-type α_1C: n=20, GGG mutant: n= 22 and 9* n=22 cardiomyocytes. Insets: Exemplar whole-cell Ca_V1.2 currents recorded from freshly dissociated cardiomyocytes of pseudo-wild-type, GGG and 9* α_1C transgenic mice. Pulses from −70 mV to +10 mV before (black traces) and 3 minutes after (red traces) 10 μM forskolin in presence of nisoldipine. (B, D, F) Graphs of conductance density-voltage relationship for nisoldipine-resistant Ca²⁺ channels recorded from pseudo-wild-type α_1C, GGG-α_1C, and 9*-α_1C before (black trace) and after (red trace) forskolin. Mean ± SEM. P<1.0 ×10⁻⁴ by repeated measures ANOVA; Sidak’s multiple comparison test P-values are in panels. (G) Fold-change in G_max. Shown are means ± SEM; P<1.0 ×10⁻⁴ by Kruskal-Wallis test; Dunn’s multiple comparison test P-values in panel. (H) Boltzmann function parameter, V₅₀. Shown are means + SEM; Paired two-tailed t-test. (I) Ratio of Ca²⁺ current after forskolin treatment to Ca²⁺ current before treatment of cardiomyocytes with forskolin for pseudo-wild-type, 9* and GGG-α_1C cardiomyocytes. Mean ± SEM. Pseudo-wild-type n=20, GGG mutant: n= 22 and 9* n=22 cardiomyocytes from at least 3 mice for each group. P<1.0 ×10⁻⁴ by Kruskal-Wallis test; Dunn’s multiple comparison test P-values in panel for pseudo-WT vs. GGG. * P<1.0 ×10^-4.