摘要
目的探讨糖尿病大鼠冠状动脉平滑肌细胞大电导钙激活钾通道(BK通道)开放概率的变化,阐明糖尿病对冠状动脉损伤的细胞电生理机制。方法将大鼠分为正常对照组和糖尿病组,分离两组大鼠冠状动脉平滑肌细胞,单通道膜内向外型膜片钳实验技术记录两组大鼠冠状动脉平滑肌细胞BK单通道电流并计算开放概率。加入BK通道激活剂DHS-1,比较正常对照组和糖尿病组大鼠冠状动脉平滑肌细胞在钙离子浓度为0.2和1μmol/L条件下BK单通道开放概率的变化。结果正常对照组和糖尿病组在刺激电压60mV和钙离子浓度0.2t.μmol/L时,BK通道开放概率分别为0.095.±0.036(n=8)和0.0032±O.0012(n=9);在钙离子浓度1μmol/L时,BK通道开放概率分别为0.458±0.077(n=5)和0.210±0.055(n=5)。两种钙离子浓度下,糖尿病组BK通道开放概率均减低(P均〈0.05)。在钙离子浓度为0.2μmol/L时,加人0.1/μmol/L的DHS-1,正常对照组BK通道开放概率增加至0.335±0.096(n=9),与未加入时比较差异有统计学意义(P〈0.05),而糖尿病组BK通道开放概率无明显变化,为0.022±0.018(/1,=8),与未加入时比较差异无统计学意义。在钙离子浓度为1μmol/L时,加入0.1μmol/L的DHS.1,正常对照组BK通道开放概率增加至0.823±0.019(/7,=5),与未加入时比较BK通道开放概率明显增加(P〈0.05),而DHS-1对糖尿病组BK通道激活作用较小,通道开放概率为0.446±0.098(n=5),但与未加入DHS.1时比较差异亦有统计学意义(P〈0.05)。结论糖尿病冠状动脉平滑肌细胞BK单通道开放概率下降可能是糖尿病冠状动脉功能损伤的重要原因。
Objective To investigate the changes of open probability (Po) of large conductance Ca^2+ -activated K^+ channel (BK channel) in diabetic coronary smooth muscle ceils and elucidate the underlying cellular electrophysiology mechanisms of coronary dysfunction. Methods Rat coronary smooth muscle cells were isolated from control group and diabetic group. BK single channel currents were recorded by patch clamp technique in inside-out configuration. Open probabilities were calculated and compared between two groups, After exposure to DHS-1, a specific BK channel activator, Po at O. 2 and 1 pLmol/L free Ca^2+ were compared between control and diabetic groups. Results In the presence of 0. 2 μmol/L free Caz+ , the Po at baseline was significantly lower in diabetic rats than in control rats (0. 0032 ±0. 0012 vs. 0. 095 ± 0. 036, P 〈 0. 05 ). Cytoplasmic application of DSH-1 significantly increased the Po to 0. 335 ± O. 096 (P 〈0. 05 vs. baseline) in control rats, whereas DSH-1 had no effect in diabetic rats (Po =0. 022± O. 018, P〉0.05 vs. baseline). In the presence of 1 μmol/L free Ca2~, the Po at baseline was also
出处
《中华心血管病杂志》
CAS
CSCD
北大核心
2012年第9期770-774,共5页
Chinese Journal of Cardiology
基金
国家自然科学基金(81070157)
江苏省自然科学基金(BK2011179)
江苏省人事厅“六大人才高峰”第七批高层次项目(006)
江苏省医学重点人才资助项目(RC2011034)
作者简介
王如兴,Email:ruxingw@yahoo.com.cn