Attenuated inhibition of L-type calcium currents by troglitazone in fructose-fed rat cardiac ventricular myocytes
Attenuated inhibition of L-type calcium currents by troglitazone in fructose-fed rat cardiac ventricular myocytes
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DOI：
10.1097/00005344-200407000-00015
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发表时间：
2004-07-01
影响因子：
3
通讯作者：
Saikawa, T
中科院分区：
文献类型：
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作者：
Arikawa, M;Takahashi, N;Saikawa, T
我们最近报道，曲格列酮（一种胰岛素增敏剂）在链脲佐菌素 (STZ) 诱导的糖尿病心室肌细胞中比年龄匹配的对照肌细胞更有效地抑制 L 型 Ca2+ 电流 (I-Ca,I-L)。然而，该药物是否能在高胰岛素血症动物模型中有效抑制 I-Ca,I-L 尚不清楚。使用全细胞电压钳技术，测量了 12 至 16 周时从富含果糖喂养的大鼠和年龄匹配的对照大鼠分离的心室肌细胞中的 I-Ca、I-L。在对照条件下，果糖喂养的肌细胞在膜电容、电流密度或 I-Ca、I-L 的电压依赖性特性方面与对照肌细胞没有差异。曲格列酮以浓度依赖性方式抑制对照和果糖喂养的肌细胞中的 I-Ca、I-L。然而，这种抑制作用在果糖喂养中比在对照肌细胞中要弱-1，在-50 mV的保持电势下测量的曲格列酮的半最大抑制浓度分别为16.9和9.8μmol/L。与 STZ 诱导的糖尿病大鼠相反，曲格列酮对心室 I-Ca、I-L 的抑制作用在果糖喂养的大鼠中减弱。血浆胰岛素浓度的持续升高可能在这些过程中发挥作用。
We recently reported that troglitazone, an insulin-sensitizing agent, inhibited L-type Ca2+ current (I-Ca,I-L) more effectively in streptozotocin (STZ)-induced diabetic ventricular myocytes than in age-matched control myocytes. However, whether this agent would effectively inhibit I-Ca,I-L in an animal model of hyperinsulinemia is unknown. Using whole-cell voltage-clamp techniques, I-Ca,I-L was measured in ventricular myocytes isolated from 12 to 16 weeks on fructose-enriched feeding and age-matched control rats. Under control conditions, fructose-fed myocytes did not differ from control myocytes in membrane capacitance, current density, or voltage-dependent properties of I-Ca,I-L. Troglitazone inhibited I-Ca,I-L in both control and fructose-fed myocytes in a concentration-dependent manner. However, this inhibition was less in fructose-fed than in control myocytes-1 the half-maximum inhibitory concentrations of troglitazone measured at a holding potential of -50 mV were 16.9 and 9.8 mumol/L, respectively. Contrary to the STZ-induced diabetic rat, the suppressive effect of troglitazone on cardiac ventricular I-Ca,I-L was attenuated in fructose-fed rats. Persistent elevation of plasma insulin concentration may play a role in these processes.