The Role of the Na+/Ca2+ Exchanger in Aberrant Intracellular Ca2+ in Cardiomyocytes of Chagas-Infected Rodents

Figures

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  Figure 1. Representative measurements of Vm and [Ca2+]d in cardiomyocytes from control and Chagas infected mice. Simultaneous measurements of membrane potential (Vm) and [Ca2+]d (A) Cardiomyocyte from control mice (Vm was -82 mV and [Ca2+]d 122 nM). (B) Cardiomyocyte from EAP-infected mice (Vm was -76mV and [Ca2+]d 200 nM). (C) Cardiomyocyte from AP-infected mice (Vm was -73 mV and [Ca2+]d 312 nM). (D) Cardiomyocyte from CP-infected mice (Vm was -69 mV and [Ca2+]d 414 nM). Vm, resting membrane potential and VCae, specific calcium potential; CONT, control mice; EAP, infected mice in the early acute phase; AP, infected mice in the acute phase; and CP, infected mice in the chronic phase. Calibration bar = 1 minute.

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  Figure 2. Resting membrane potential, diastolic [Ca2+] and [Na+] in cardiomyocytes from control and Chagas infected mice. (A) The resting membrane potential, (B) [Ca2+]d, and (C) [Na+]d were measured in quiescent cardiomyocytes from CONT mice (ncells =24 and nmice =3), EAP-infected mice (ncells =19 and nmice =3), AP-infected mice (ncells =21 and nmice =3) and CP-infected mice (ncells =18 and nmice =5). Data are expressed as means ± S.D. Statistical analysis was performed using one-way ANOVA, followed by Tukey’s multiple comparison tests, *p < 0.05; ***p < 0.001. CONT, control mice; EAP, early acute phase of infected mice; AP, acute phase of infected mice; and CP, chronic phase of infected mice.

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  Figure 3. Effects of reduction in [Na+]e on [Ca2+]d in cardiomyocytes from control and Chagas infected mice. [Ca2+]d was measured before and after cardiomyocyte treatments with solutions in which [Na+]e was partially or completely replaced with NMG. [Ca2+]d was determined in quiescent cardiomyocytes from CONT mice (ncells =13-24 and nmice =4), EAP-infected mice (ncells =12-19 and nmice =5), AP-infected mice (ncells =12-21 and nmice =5) and CP-infected mice (ncells =6-18 and nmice =9). Data are expressed as means ± S.D. Statistical analysis was performed as described above, ***p < 0.001. CONT, control mice; EAP, early acute phase of infected mice; AP, acute phase of infected mice; and CP, chronic phase of infected mice.

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  Figure 4. Effect extracellular Ca2+ on Na+ depletion-induced elevation of [Ca2+]d. [Ca2+]d was measured in cardiomyocytes from CONT, EAP-, AP-, and CP-infected mice in normal Tyrode, Ca2+-free Tyrode solution, and Ca2+ and Na+ free Tyrode solution. [Ca2+]d was determined in quiescent cardiomyocytes from CONT (ncells =16-24 and nmice =4), EAP-infect mice (ncells =15-19 and nmice =5), AP-infect mice (ncells =18-21 and nmice =6) and CP-infect mice (ncells =15-18 and nmice =8). Data are expressed as mean ± S.E. Statistical analysis was performed as described above, *** p < 0.001. CONT, control mice; EAP, early acute phase of infected mice; AP, acute phase of infected mice; and CP, chronic phase of infected mice. ns, no significant.

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  Figure 5. NCX blockers inhibited Na+ withdraw-induced [Ca2+]d increases in cardiomyocytes from control and Chagas infected mice. (A) Effects of KB-R7943 and (B) YM-244769 on [Ca2+]d increases caused by Na+ removal. [Ca2+]d was determined in (i) normal Tyrode solution (ii) after 10 min of incubation with 10 μm KB-R7943) or 1 µM YM-244769 and (iii) after incubation, either KB-R7943 in Na+ free solution or YM-244769 in Na+ free solution. Experiments were carried out in cardiomyocytes from CONT (ncells=15-24 and nmice=6), EAP (ncells=12-19 and nmice=8), AP (ncells=13-21 and nmice=8) and CP cardiomyocytes (ncells=11-18 and nmice=9). Data are expressed as mean ± S.E. Statistical analysis was performed as described above, ***p < 0.001. CONT: control mice; EAP: early acute phase of infected mice; AP: acute phase of infected mice; and CP: chronic phase of infected mice.