Effects of L-type Ca2+ channel modulation on direct myocardial effects of diazepam and midazolam in adult rat ventricular myocytes

被引：8
作者：
Kanaya N. [1 ]
Murray P.A. [2 ]
Damron D.S. [2 ]
机构：
[1] Department of Anesthesiology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8643, S-1
[2] Center for Anesthesiology Research, The Cleveland Clinic Foundation, Cleveland, OH
来源：
Journal of Anesthesia | 2006年 / 20卷 / 1期
关键词：
Benzodiazepines; Cellular mechanisms; Heart; Inotropes; L-type Ca[!sup]2+[!/sup] channel;
D O I：
10.1007/s00540-005-0356-7
中图分类号：
学科分类号：
摘要：
Purpose. Our objective was to determine whether an L-type Ca2+ channel modulation could alter myocardial depression induced by midazolam or diazepam in adult rat ventricular myocytes. Methods. Freshly isolated rat ventricular myocytes were loaded with fura-2/AM and field-stimulated (0.3 Hz) at 28°C. Amplitude and timing of intracellular Ca2+ concentration ([Ca2+]i) and myocyte shortening were simultaneously monitored in individual cells. Results. Midazolam (3-100μM) caused a decrease in both peak [Ca2+]i and shortening. Diazepam (30, 100μM) increased myocyte shortening and peak [Ca2+]i; however, higher concentration of diazepam (300μM) decreased shortening and peak [Ca2+]i. Bay K 8644 (0.01-10μM), an L-type Ca2+ channel agonist, caused dose-dependent increases in peak [Ca2+]i and shortening. In contrast, verapamil (0.1-50μM), an L-type Ca2+ channel antagonist, caused dose-dependent decreases in peak [Ca2+]i and shortening. Dose-response curves to benzodiazepines on peak [Ca2+]i and shortening were not affected by pretreatment with Bay K 8644 (0.1μM) or verapamil (1μM). Diazepam (30, 100μM), but not midazolam (3-30μM), increased shortening and [Ca2+]i in the presence or absence of L-type Ca2+ channel modulators. Diazepam (30μM) and midazolam (10μM) had no effect on peak [Ca2+]i of a caffeine-induced [Ca2+] i transient, which was used as a measure of SR Ca2+ content. Conclusion. Midazolam and diazepam have differential effects on cardiac E-C coupling. Diazepam, but not midazolam, enhances cardiac E-C coupling independent of L-type Ca2+ channel modulation. © JSA 2006.
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页码：17 / 25
页数：8
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