Abstract
Objective To investigate the effects of aconitine, mesaconitine and hypaconitine on calcium release in isolated adult rat cardiac myocytes. Methods The left ventricular cardiac myocytes isolated from adult Sprague-Dawley rats were perfused with acnitine, mesaconitine and hypaconitine at 0.3 μmol/L, 1 μmol/L, 3 μmol/L for 12 min. The spontaneous calcium release (SCR) rate, the end-diastolic [Ca2+] (F0) and the calcium transient amplitude (ΔF) were detected 4 min, 8 min and 12 min after the perfusion. 12 min after the perfusion with acnitine, mesaconitine and hypaconitine at 0.3 μmol/L, the changes of systolic dynamics and calcium transient were detected for the positive inotropic effect. Results Any of aconitine, mesaconitine and hypaconitine induced SCR, mesconitine- induced SCR rate was highest at low concentration (0.3 μmol/L), and aconitine-induced SCR rate highest at high concentration (3 μmol/L). Compared with the control, 12 min after the perfusion with acnitine, mesaconitine and hypaconitine at 3 μmol/L elevated F0 (1.459 ± 0.379, 1.585 ± 0.493, 1.213 ± 0.254 vs. 1.079 ± 0.108, all P<0.05) and ΔF(1.615 ± 0.455, 2.210 ± 0.756, 1.528 ± 0.422 vs. 1.036 ± 0.125, all P<0.05), mesaconitine with ΔF higher than aconitine and hypaconitine. At low concentration (0.3 μmol/L), compared with control, aconitine, mesaconitine and hypaconitine increased ΔF (0.409 ± 0.127, 0.423 ± 0.107, 0.414 ± 0.118 vs. 0.260 ± 0.065; P<0.05 or P<0.01) and contraction amplitudes (5.464% ± 2.239%, 7.449% ± 2.548%, 5.524% ± 1.645% vs. 3.428% ± 0.911%; P<0.05 or P<0.01), prolonged the time to peak of calcium transient (0.041 ± 0.016 s, 0.039 ± 0.009 s, 0.038 ± 0.011 s vs. 0.032 ± 0.007 s; P<0.05 or P<0.01); compared with aconitine, mesaconitine and hypaconitine decreased calcium transient time constant (0.301 ± 0.054 s, 0.324 ± 0.064 s vs. 0.361 ± 0.076 s; P<0.05 or P<0.01) and diastolic t50 (0.124 ± 0.035 s, 0.126 ± 0.040 s vs. 0.157 ± 0.056 s; P<0.05 or P<0.01). Conclusions Aconitine, mesaconitine and hypaconitine reveal the positive inotropic effects couple with the toxic effects. Increased [Ca2+] in cardiac myocytes is the key factor for the positive inotropic effects, but also the risk factor for SCR. Key words: Calcium; Myocytes, cardiac; Drugs, Chinese herbal; Aconitine; Rats; Mesaconitine; Hypaconitine
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