中国药理学与毒理学杂志
中國藥理學與毒理學雜誌
중국약이학여독이학잡지
CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY
2009年
3期
168-175
,共8页
张伟%苗庆峰%苏素文%程佳依%王燕婷%张永健
張偉%苗慶峰%囌素文%程佳依%王燕婷%張永健
장위%묘경봉%소소문%정가의%왕연정%장영건
双苯氟嗪%心室%肌细胞%心脏%膜片钳技术%钠电流
雙苯氟嗪%心室%肌細胞%心髒%膜片鉗技術%鈉電流
쌍분불진%심실%기세포%심장%막편겸기술%납전류
dipfluzine%heart ventricles%myocytes,cardiac%patch-clamp techniques%sodium current
目的 观察双苯氟嗪对豚鼠心室肌细胞膜钠电流的影响.方法 用酶解方法分离豚鼠心室肌细胞,全细胞膜片钳技术记录钠电流.结果 将细胞钳制在-80 mV,给(-80～+50) mV,50 ms和步阶10 mV的去极化脉冲,记录到的电流被河豚毒素10 μmol·L-1完全抑制.在该刺激条件下,该电流最大激活电压在-20 mV左右,翻转电压在+30 mV左右,提示该电流为钠电流.双苯氟嗪可以浓度依赖性地抑制钠电流.双苯氟嗪对钠电流的抑制作用在冲洗后可部分恢复,表明其对钠通道的抑制作用具有可逆性. 双苯氟嗪可使钠电流I-V曲线上移,但对钠电流的电压依赖性特征、最大激活电压和翻转电压无明显影响.在双苯氟嗪40 μmol·L-1存在下,最大激活电压下的峰值电流下降约46%;双苯氟嗪可明显使钠电流稳态失活曲线左移,但不影响曲线的斜率因子.双苯氟嗪40 μmol·L-1可使钠电流半数失活电压从(-73.0±4.6) mV减少到(-82.8±7.2) mV.但双苯氟嗪对钠电流稳态激活无明显影响,在双苯氟嗪40 μmol·L-1存在下,半数激活电压(-33.7±3.6 )mV和斜率因子(5.6±2.4) mV与对照组激活电压(-34.9±5.1) mV和斜率因子(6.0±4.8)mV相比无显著性差异.双苯氟嗪可以使钠电流从失活状态下恢复明显减慢,双苯氟嗪40 μmol·L-1可使恢复时间常数延长[(79±28) vs (36±11) ms].结论 双苯氟嗪可以浓度依赖性、使用依赖性和频率依赖性地抑制心肌钠电流,并且主要作用于钠电流的失活状态.
目的 觀察雙苯氟嗪對豚鼠心室肌細胞膜鈉電流的影響.方法 用酶解方法分離豚鼠心室肌細胞,全細胞膜片鉗技術記錄鈉電流.結果 將細胞鉗製在-80 mV,給(-80～+50) mV,50 ms和步階10 mV的去極化脈遲,記錄到的電流被河豚毒素10 μmol·L-1完全抑製.在該刺激條件下,該電流最大激活電壓在-20 mV左右,翻轉電壓在+30 mV左右,提示該電流為鈉電流.雙苯氟嗪可以濃度依賴性地抑製鈉電流.雙苯氟嗪對鈉電流的抑製作用在遲洗後可部分恢複,錶明其對鈉通道的抑製作用具有可逆性. 雙苯氟嗪可使鈉電流I-V麯線上移,但對鈉電流的電壓依賴性特徵、最大激活電壓和翻轉電壓無明顯影響.在雙苯氟嗪40 μmol·L-1存在下,最大激活電壓下的峰值電流下降約46%;雙苯氟嗪可明顯使鈉電流穩態失活麯線左移,但不影響麯線的斜率因子.雙苯氟嗪40 μmol·L-1可使鈉電流半數失活電壓從(-73.0±4.6) mV減少到(-82.8±7.2) mV.但雙苯氟嗪對鈉電流穩態激活無明顯影響,在雙苯氟嗪40 μmol·L-1存在下,半數激活電壓(-33.7±3.6 )mV和斜率因子(5.6±2.4) mV與對照組激活電壓(-34.9±5.1) mV和斜率因子(6.0±4.8)mV相比無顯著性差異.雙苯氟嗪可以使鈉電流從失活狀態下恢複明顯減慢,雙苯氟嗪40 μmol·L-1可使恢複時間常數延長[(79±28) vs (36±11) ms].結論 雙苯氟嗪可以濃度依賴性、使用依賴性和頻率依賴性地抑製心肌鈉電流,併且主要作用于鈉電流的失活狀態.
목적 관찰쌍분불진대돈서심실기세포막납전류적영향.방법 용매해방법분리돈서심실기세포,전세포막편겸기술기록납전류.결과 장세포겸제재-80 mV,급(-80～+50) mV,50 ms화보계10 mV적거겁화맥충,기록도적전류피하돈독소10 μmol·L-1완전억제.재해자격조건하,해전류최대격활전압재-20 mV좌우,번전전압재+30 mV좌우,제시해전류위납전류.쌍분불진가이농도의뢰성지억제납전류.쌍분불진대납전류적억제작용재충세후가부분회복,표명기대납통도적억제작용구유가역성. 쌍분불진가사납전류I-V곡선상이,단대납전류적전압의뢰성특정、최대격활전압화번전전압무명현영향.재쌍분불진40 μmol·L-1존재하,최대격활전압하적봉치전류하강약46%;쌍분불진가명현사납전류은태실활곡선좌이,단불영향곡선적사솔인자.쌍분불진40 μmol·L-1가사납전류반수실활전압종(-73.0±4.6) mV감소도(-82.8±7.2) mV.단쌍분불진대납전류은태격활무명현영향,재쌍분불진40 μmol·L-1존재하,반수격활전압(-33.7±3.6 )mV화사솔인자(5.6±2.4) mV여대조조격활전압(-34.9±5.1) mV화사솔인자(6.0±4.8)mV상비무현저성차이.쌍분불진가이사납전류종실활상태하회복명현감만,쌍분불진40 μmol·L-1가사회복시간상수연장[(79±28) vs (36±11) ms].결론 쌍분불진가이농도의뢰성、사용의뢰성화빈솔의뢰성지억제심기납전류,병차주요작용우납전류적실활상태.
AIM To investigate effect of dipfluzine on sodium current (INa+) in isolated single guinea-pig ventricular myocytes. METHODS INa+ was measured by whole cell patch-clamp technique in single isolated guinea-pig ventricular myocytes which were prepared by enzymatic dissociation method. RESULTSCardiac INa+ was elicited by 50-ms pulses to +50 mV from holding potential at -80 mV with a step of +10 mV, which could be blocked completely by tetrodotoxin 10 μmol·L-1. The peak INa+ occurred at about -20 mV and the reversal potential for INa+ was about +30 mV. Dipfluzine inhibited cardiac INa+ in a concentration-dependent manner. The blocking effect of dipfluzine on INa+ was reversible. Dipfluzine suppressed cardiac INa+, without modifying maximum activation potential and reversal potential. The peak of INa+ was decreased by about 46% at -20 mV and shape of I-V curve was not altered by dipfluzine 40 μmol·L-1. Dipfluzine shifted the steady-state inactivation curve of INa+ towards more negative without changing the slope factor and produced very little change in the steady-state activation curve towards more positive. The mean half activation voltage was (-34.9±5.1) mV and slope factor was (6.0±4.8) mV under control condition and (-33.7±3.6) mV and (5.6±2.4) mV following exposure to dipfluzine 40 μmol·L-1. The half inactivation voltage was (-73.0±4.6)mV and slope factor was (4.8±1.8)mV under control condition and (-82.8±7.2)mV and (4.8±1.8)mV following dipfluzine 40 μmol·L-1 treatment. Dipfluzine delayed recovery of cardiac INa+ from inactivation state. The time course of recovery was (36±11) ms in control group and (79±28) ms in dipfluzine 40 μmol·L-1 group. CONCLUSION Dipfluzine inhi- bits cardiac INa+ in a concentration-dependent manner and has higher affinity for the inactivated state than that for resting state of Na+ channels.
