Effects of aconitine, mesaconitine and hypaconitine on calcium release in isolated adult rat cardiac myocytes

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