Restitution of twitches, L-type Ca²⁺ current, Ca²⁺ transients, and SR Ca²⁺ load in ventricular myocardium. All restitution curves are fitted by a single exponential to obtain restitution rates (1/τ). (A) Average mechanical restitution curves from nine WT (n = 7) and nine R4496C (n = 8) ventricular trabeculae and L-type Ca²⁺ current recovery curves from 15 WT (n = 3) and 14 R4496C (n = 3) myocytes are shown superimposed. Rates for mechanical restitution: 1.96 ± 0.11 s⁻¹ in WT and 2.63 ± 0.34 s⁻¹ in R4496C; P < 0.01. Rates for L-type Ca²⁺ current recovery: 8.68 ± 0.35 s⁻¹ in WT and 8.79 ± 0.41 s⁻¹ in R4496C; P = 0.51. (B) Average curves showing the restitution of Ca²⁺-transient amplitude in 21 WT (n = 4) and 23 R4496C (n = 5) ventricular myocytes. Rates: 3.72 ± 0.34 s⁻¹ in WT and 5.33 ± 0.64 s⁻¹ in R4496C; P < 0.05. (C) Representative examples of simultaneous intracellular Ca²⁺-transient and membrane current recordings during rapid application of 20 mM caffeine at different premature intervals. (Inset) Caffeine-induced Ca²⁺ transient obtained by subtracting the average shape of the preceding regular Ca²⁺ transients from the fused traces. (D) SR Ca²⁺ load recovery curves calculated from both the amplitude of caffeine-induced Ca²⁺ transient and the integration of inward NCX current. Data are derived from 13 WT (n = 3) and 15 R4496C (n = 3) myocytes. Rates calculated from caffeine-induced Ca²⁺ transient: 7.15 ± 0.21 s⁻¹ in WT and 7.71 ± 0.29 s⁻¹ in R4496C; P = 0.48. Rates calculated from integration of the inward NCX current: 8.63 ± 0.23 s⁻¹ in WT and 8.74 ± 0.31 s⁻¹ in R4496C; P = 0.48. Error bars represent mean ± SEM.