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白藜芦醇对豚鼠心室肌细胞L型钙通道的影响

Effects of resveratrol on L-type calcium current (ICa-L) in guinea pig ventricular myocytes

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【作者】 刘妍妍白云龙王涛杜娟张妍李宝馨吕延杰杨宝峰

【Author】 LIU Yan-yan,BAI Yun-long,WANG Tao,DU Juan; ZHANG Yan,LI Bao-xin,Lv Yan-jie,YANG Bao-feng (Dept of Pharmacology,Haerbin Medical University,Bio-pharmaceutical Key Laboratory of Heilongjiang Province,Haerbin 150086,China)

【机构】 哈尔滨医科大学药理学教研室黑龙江省生物医药重点试验室哈尔滨医科大学药理学教研室黑龙江省生物医药重点试验室 黑龙江哈尔滨150086黑龙江哈尔滨150086

【摘要】 目的研究白藜芦醇(resveratrol,RES)对豚鼠心室肌细胞L型钙通道的影响。方法酶解法分离单个豚鼠心室肌细胞,采用全细胞膜片钳技术记录白藜芦醇对豚鼠单个心室细胞L型钙通道电流(ICa-L)的影响。结果不同浓度的RES明显抑制ICa-L,1、10、100μmol.L-1L的RES使其峰电流密度从(12.96±1.48)pA/pF减少到(11.36±1.59)、(9.96±1.51)和(7.77±0.68)pA/pF(n=6,P<0.01),冲洗后可恢复至(11.85±0.83)pA/pF。RES可使ICa-L的I-U关系曲线上移,其形状和峰值电压保持不变;RES还可使通道的激活曲线右移,但失活曲线和失活恢复时间无改变。结论白藜芦醇通过延长L型钙通道激活过程而明显抑制ICa-L,减少细胞外的钙离子内流,延长有效不应期,从而发挥抗心律失常作用。

【Abstract】 Aim To investigate effects of different concentrations of resveratrol (RES) on L-type calcium channels in guinea pig ventricular myocytes. Methods Enzyme digestion was used to isolate single ventricular myocyte and whole cell patch clamp technique was used to record L-type calcium current. Results RES inhibited ICa-L in a concentration- dependent manner .The application of 1、10、100 μmol·L-1 RES reduced the density of peak ICa-L from ( -12.96±1.48 ) pA/pF to (-11.36±1.59)pA/pF (n= 6,P<0.01), (-9.96±1.51) pA/pF (n= 6, P< 0.01) and (-7.77±0.68) pA/pF (n= 6,P<0.01) pA/pF at 0 mV, respectively.ICa-L came back to (-11.85±0.83) pA/pF after washout. RES remarkably shifted activation curve to the right, and delayed the voltage-dependent steady-state activation of calcium current. The half activation potential (V1/2) was ( -32.32801±0.366 )mV in the control and(-23.36414±0.94711)mV in the presence of RES 1 μmol·L-1. The slope factor(k) was (8.86352±0.37865) in the control and (8.7592±0.8847 ) in the presence of RES 1 μmol·L-1(n= 6,P<0.05). Steady-state inactivation curve was not affected markedly, also V1/2 value and k value in the presence of RES 1 μmol·L-1 were not markedly different from those of the control. The recovery time from inactivation was not changed significantly. Conclusion RES decreased the amplitude of L-type calcium current, which would be one of cardiac protection mechanisms of the drug. And slowing the activation procession of ICa would help to its cardiac protection.

【基金】 国家自然科学基金重点资助项目(No30430780);国家自然科学基金面上资助项目(No30371647)
  • 【文献出处】 中国药理学通报 ,Chinese Pharmacological Bulletin , 编辑部邮箱 ,2007年02期
  • 【分类号】R285
  • 【被引频次】21
  • 【下载频次】408
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