Berberine elicits anti-arrhythmic effects via IK1/Kir2.1 in the rat type 2 diabetic myocardial infarction model.
The purpose of this study was to explore the anti-arrhythmic mechanisms of berberine in diabetic rats with myocardial infarction. Sixty rats were divided into four groups: (1) normal control; (2) myocardial infarction group (MI); (3) Type 2 diabetes with myocardial infarction group (T2DM+MI); and (4) Type 2 diabetic with myocardial infarction berberine-treated group (BBR). Berberine (60 mg/kg/day) was administered after coronary artery ligation in the T2DM+MI group for 14 days. Currents were measured using whole-cell patch-clamp techniques. Western blot was performed for quantification of target proteins. The study showed that arrhythmias induced by myocardial infarction were aggravated in diabetic rats. Arrhythmia scores in the MI group were significantly higher than in the control group. Interestingly, the administration of berberine at a dose of 60 mg/kg/d recovered arrhythmia scores (P > 0.05). RMP (Resting membrane potential) which could be recovered by berberine (P < 0.05), was significantly reduced in both the infarction groups. I(K1) current and current density markedly decreased in the MI and T2DM+MI groups (P < 0.05) and could be reversed by berberine (P < 0.05). The relative expression of Kir2.1 in rats in the MI and T2DM+MI group were both significantly decreased (P < 0.05); berberine recovered depressed Kir2.1 to nearly normal levels. The results suggest that the effects of berberine on I(K1)/Kir2.1 may be an important mechanism for producing anti-arrhythmic effects.
Wang
Li-hong
LH
Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. nd6688@163.com
Yu
Chang-hua
CH
Fu
Ying
Y
Li
Qiang
Q
Sun
Yu-qian
YQ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001599:Berberine / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D001599:Berberine; D011188:Potassium