Calcium Overload or Underload? The Effects of Doxorubicin on the Calcium Dynamics in Guinea Pig Hearts

Figures

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  Figure 1. (A) schematic diagram showing the mapping region and the location of the pacing stimulator. (B) Consecutive mapping of the Ca2+ fluorescence signal. The sampling frequency was 800 frames/second. For clarity, only the 1st, 900th and 1600th frames are displayed. (C) Plot of the averaged fluorescence intensity of each frame in (B) (Y axis) versus the number of frames (X axis).

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  Figure 2. (A–D) the effect of DOXO on Ca-AP-Lag, MRV_Ca, MFV_Ca and CaD50 in sinus and tachypaced groups. (A) in the sinus group, 3 µM and 10 µM DOXO significantly prolonged the Ca-AP-Lag (p < 0.01); in the paced group, low concentration of DOXO (1 µM and 3 µM) had the opposite effect to that of 10 µM DOXO. (B) the MRV_Ca was decreased by DOXO (1 µM, 10 µM and 3 µM, p < 0.01) in the sinus group but increased in the tachypaced group by DOXO (1 µM and 3 µM, p < 0.05). (C) the MFV_Ca was decreased by DOXO (3 µM, p < 0.01 and 10 µM, p < 0.05) in the sinus group, but increased by DOXO (1 µM and 3 µM, p < 0.01) in the tachypaced group. (D) The CaD50 was decreased by DOXO (3 µM, p < 0.05 and 10 µM, p < 0.01) in the sinus group, but was increased by DOXO (10 µM, p < 0.01) in the tachypaced group. Ca-AP-Lag: the time difference between the peak of AP and the peak of the following Ca2+ signal; MRV_Ca and MFV_Ca: the maximum rising and following velocity of the Ca2+ signal; CaD50: the duration of the Ca2+ signal at 50% of the amplitude. ΔF: change in the fluorescence intensity.

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  Figure 3. (A,B) An example mapping of the Ca2+ signal duration at 50% amplitude (CaD50) before (A) and after (B) the application of DOXO 10 µM in a heart with sinus rhythm. (C) The standard deviation (STD) of CaD50 in the sinus and paced groups. In the sinus group, DOXO 3 µM and 10 µM significantly increased the STD (p < 0.01), and in the paced group, DOXO 10 µM significantly increased the STD (p < 0.01). Compared to the sinus group, tachypacing (300 bpm) increased the STD (p < 0.01, sinus control vs. paced control).

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  Figure 4. (A,B) The correlation of MRV_Ca and MFV_Ca in sinus group (A) and paced group. (C–J) the correlation of Ca-AP-Lag with the peak of Ca2+ signal ((C): sinus, (D): paced), CaD50 ((E): sinus, (F): paced), MRV ((G): sinus, (H): paced) and MFV ((I): sinus, (J): paced). All the correlations were performed with Pearson analysis and were significant (p < 0.01); and the equation Y = A × X ± B was employed to describe the simple linear regression (insets in each Figure).