Enhanced inhibition of L-type calcium currents by troglitazone in streptozotocin-induced diabetic rat cardiac ventricular myocytes
Enhanced inhibition of L-type calcium currents by troglitazone in streptozotocin-induced diabetic rat cardiac ventricular myocytes
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DOI：
10.1038/sj.bjp.0704757
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发表时间：
2002-07-01
影响因子：
7.3
通讯作者：
Sakata, T
中科院分区：
文献类型：
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作者：
Arikawa, M;Takahashi, N;Sakata, T
1曲格列酮是一种胰岛素增敏剂，可改善实验动物和糖尿病患者的心功能，抑制心肌细胞电压依赖性L型钙电流(I-Ca，I-L)，这可能是其心脏保护作用的基础。采用全细胞电压钳技术，测定了链脲佐菌素诱导的4-6周糖尿病大鼠和年龄匹配对照大鼠分离的心肌细胞的I-Ca，I-L。3在氯化铯内液的对照条件下，糖尿病心肌细胞的膜电容、电流密度和电压依赖性与对照组无差异，I-L.4曲格列酮以浓度依赖的方式降低对照组和糖尿病大鼠心肌细胞的I-Ca幅值，i-L。这种抑制作用在糖尿病大鼠心肌细胞中更为明显；在保持电位为-50 mV时，曲格列酮的半数抑制浓度分别为4.3m ol和9.5m ol L(-1)。5曲格列酮在5 m ol L(-1)时对对照组和糖尿病心肌细胞的稳态失活电压依赖性和i-Ca、i-L的失活时间均无明显影响。6由于曲格列酮对STZ诱导的糖尿病心肌细胞的i-Ca有更有效的抑制作用，I-L可更有效地预防糖尿病心功能不全。
1 Troglitazone, an insulin-sensitizing agent shown to improve cardiac function in both experimental animals and patients with diabetes, inhibits voltage-dependent L-type Ca2+ currents (I-Ca,I-L) in cardiac myocytes, which may underlie its cardioprotective effects. However, inhibition by troglitaizone of I-Ca,I-L in diabetic cardiac myocytes has not been characterized.2 Using whole-cell voltage-clamp techniques, I-Ca,I-L was measured in ventricular myocytes isolated from 4-6 weeks streptozotocin (STZ)-induced diabetic rats and age-matched control rats.3 Under control conditions with CsCl internal solution, diabetic myocytes did not differ from control myocytes in membrane capacitance, current density or voltage-dependent properties of I-Ca,I-L.4 Troglitazone decreased amplitude Of I-Ca,I-L in both control and diabetic myocytes in a concentration-dependent manner. This inhibition was more potent in diabetic than in control myocytes; half-maximum inhibitory concentrations of troglitazone measured at a holding potential of -50 mV were 4.3 and 9.5 mumol l(-1), respectively.5 Troglitazone at 5 mumol l(-1) did not significantly influence the voltage dependency of steady-state inactivation or the inactivation time course of I-Ca,I-L in either control or diabetic myocytes.6 Since troglitazone inhibits I-Ca,I-L more effectively in STZ-induced diabetic ventricular myocytes, this agent may prevent cardiac dysfunction in diabetes.