Differential modulation of the cardiac L- and T-type calcium channel currents by isoflurane
Differential modulation of the cardiac L- and T-type calcium channel currents by isoflurane
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DOI：
10.1097/00000542-200108000-00038
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发表时间：
2001-08-01
期刊：
影响因子：
8.8
通讯作者：
Bosnjak, ZJ
中科院分区：
文献类型：
--
作者：
Camara, AKS;Begic, Z;Bosnjak, ZJ
背景：挥发性麻醉剂通过抑制L型和t型钙通道发挥负性变时性和收缩性作用。本研究考察并比较了异氟醚对心房L型和t型钙电流（I-Ca，I-L和I-Ca，I-T）和心室I-Ca，I-L的剂量依赖性影响。方法：从酶分离的豚鼠心肌细胞中记录全细胞I-Ca。心房和心室I-Ca、I-L的电流-电压关系由-90和-50 mV的保持电位得到，以10 mV的增量测试+60 mV的电位。心房I-Ca，I-T通过减去-50和-90 mV保持电位获得的电流来确定。稳态失活是用标准的双脉冲协议确定的，数据用玻尔兹曼方程拟合。结果：异氟醚对心房I-Ca、I-T、I-Ca、I-L和心室I-Ca、I-L的K-d值分别为0.23 +/- 0.03、0.34 +/- 0.03和0.71 +/- 0.02 mM，呈剂量依赖性抑制ICa，并在稳态失活时引起显著的超极化偏移（P < 0.05）。在1.2和1.6 nam时，异氟醚引起心室I-Ca、I-L稳态激活的去极化移位显著（P < 0.05），而心房I-Ca、I-L或I-Ca、I-T稳态激活的去极化移位不显著。除了抑制I-Ca、I-L外，异氟醚还引起心房和心室l型钙通道I-Ca逆转电位的超极化移位。结论：心房I-Ca、I-T对异氟醚的敏感性高于心房I-Ca、I-L和心室I-Ca，其中I-L对麻醉反应最小。心房和心室钙通道的不同敏感性可能反映了钙通道的表型差异或麻醉调节的差异。
Background: Volatile anesthetics exert their negative chronotropic and inotropic effects, in part by depressing the L- and T-type calcium channels. This study examines and compares the dose-dependent effects of isoflurane on atrial L- and T-type calcium currents (I-Ca,I-L and I-Ca,I-T) and ventricular I-Ca,I-L.Methods: Whole cell I-Ca was recorded from enzymatically isolated guinea pig cardiomyocytes. Current-voltage relations for atrial and ventricular I-Ca,I-L was obtained from holding potentials of -90 and -50 mV to test a potential of +60 mV in 10-mV increments. Atrial I-Ca,I-T was determined by subtraction of currents obtained from holding potentials of -50 and -90 mV. Steady state inactivation was determined using standard two-pulse protocols, and data were fitted with the Boltzmann equation.Results: Isoflurane depressed ICa in a dose-dependent manner, with K-d values of 0.23 +/- 0.03, 0.34 +/- 0.03, and 0.71 +/- 0.02 mM of anesthetic for atrial I-Ca,I-T and I-Ca,I-L and ventricular I-Ca,I-L, respectively, and caused a significant (P < 0.05) hyperpolarizing shift in steady state inactivation. At 1.2 and 1.6 nam, isoflurane caused a significant (P < 0.05) depolarizing shift in the steady state activation in ventricular I-Ca,I-L but not in atrial I-Ca,I-L or I-Ca,I-T. In addition to the depression of I-Ca,I-L, isoflurane also induced a hyperpolarizing shift in the reversal potential of I-Ca for both atrial and ventricular L-type calcium channels.Conclusion: The results show that atrial I-Ca,I-T is more sensitive to isoflurane than atrial I-Ca,I-L, and ventricular I-Ca,I-L Was the least responsive to the anesthetic. These differential sensitivities of the calcium channels in the atrial and ventricular chambers might reflect phenotypic differences in the calcium channels or differences in modulation by the anesthetic.