RESUMEN
The present study was designed to elucidate the potential mechanism underlying that berberine suppressed ischemic arrhythmias in a rat model of diabetes mellitus (DM). Streptozotocin (STZ)-induced diabetic rats were subjected to ischemia by the occlusion of left anterior descending (LAD) coronary artery. Berberine was orally administered for 7 days before ischemic injury in diabetic rats. Whole-cell patch-clamp was performed to measure the transient outward K⺠current (I(to)) and L-type Ca²âº current (I(Ca)). Results showed that oral administration of berberine (100 mg/kg) attenuated ischemia-induced arrhythmias in diabetic rats. Berberine significantly shortened the prolonged QTc interval from 214 ± 6ms to 189 ± 5ms in ischemic diabetic rats, and also restored the diminished I(to) and I(Ca) current densities in the same animal model rats. In conclusion, the ability of berberine to protect diabetic rats against cardiac arrhythmias makes it possible to be a prospective therapeutic agent in clinical management of cardiac disease secondary to diabetes.
Asunto(s)
Arritmias Cardíacas/tratamiento farmacológico , Berberina/administración & dosificación , Canales de Calcio Tipo L/metabolismo , Infarto del Miocardio/tratamiento farmacológico , Canales de Potasio/metabolismo , Administración Oral , Animales , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patología , Berberina/farmacología , Calcio/metabolismo , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Diabetes Mellitus Experimental/fisiopatología , Fenómenos Electrofisiológicos , Masculino , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocitos Cardíacos/metabolismo , Técnicas de Placa-Clamp , Potasio/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
AIM: To determine the effects of cyclovirobuxine D (CD) on intracellular Ca2+ mobilization and L-type Ca2+ current (I(Ca-L)) in isolated rat cardiomyocytes. METHODS: The effects of CD on the amplitude of I(Ca-L) and intracellular Ca2+ mobilization induced by KCl and caffeine were studied with the method of patch-clamp technique and laser scanning confocal microscopy in rat ventricular myocytes. RESULTS: CD decreased the amplitude of I(Ca-L) in a concentration-dependent manner. At 10 mV, 1 and 10 micromol x L(-1) CD decreased I(Ca-L) density from (- 9.9 +/- 1.8) pA/pF to (-6.4 +/- 1.4) and (-4.2 +/- 0.6) pA/pF, respectively. Confocal experiments showed that intracellular fluorescent intensity (FI) value of [Ca2+] in control resting level was not changed by 1 and 10 micromol x L(-1) CD. [Ca2+] increase in response to KCl could not be reduced by CD. The rise of [Ca2+]i in response to caffeine was further enhanced by pretreatment with CD. CONCLUSION: CD decreased I(Ca,L) in a concentration-dependent manner and increased [Ca2+]i release induced by caffeine in rat ventricular cardiomyocytes.