Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs.
Reduced L-type calcium current in ventricular myocytes from endotoxemic guinea pigs.
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DOI：
10.1152/ajpheart.1997.273.5.h2312
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发表时间：
1997-11
期刊：
影响因子：
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通讯作者：
J. Zhong;T. Hwang;H. R. Adams;L. Rubin
中科院分区：
文献类型：
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作者：
J. Zhong;T. Hwang;H. R. Adams;L. Rubin
对革兰氏阴性脓毒症及其实验对应物内毒素血症的循环反应包括心肌收缩力的严重功能障碍，该功能障碍存在于心肌细胞中，并与收缩期细胞内游离Ca 2+浓度（[Ca 2 +]i）降低相关。我们探讨了内毒素血症心肌细胞收缩期[Ca ~（2+）] i降低与L型Ca ~（2+）电流（ICa，L）降低相关的可能性。豚鼠腹腔注射大肠杆菌脂多糖（LPS; 4 mg/kg）后4 h分离心室肌细胞。采用全细胞膜片钳方法测定细胞膜电位和钙电流。内毒素血症心肌细胞动作电位时程明显短于对照组（50%复极时间：内毒素组314 ± 23 ms，对照组519 ± 36 ms，P < 0.05）。相应地，内毒素血症心肌细胞的峰值ICa，L密度（3.5 ± 0.2pA/pF）和Ba 2+电流（IBa）密度（7.3 ± 0.5pA/pF）均显著低于对照组（ICa，L密度6.1 ± 0.3pA/pF，IBa密度11.3 ± 0.8pA/pF; P < 0.05）。内毒素血症诱导的峰值I Ca，L降低不能归因于电流-电压关系、稳态激活和失活或失活恢复的改变。β-肾上腺素受体激动剂异丙肾上腺素（isoproterenol）可逆转LPS引起的ICa，L峰值、细胞收缩和收缩期[Ca ~（2+）]i的降低，而钙通道激活剂BAY K 8644则不能。这些数据表明，宿主对内毒素血症的部分反应涉及心室肌细胞肌膜I Ca，L减少。
The circulatory response to gram-negative sepsis and its experimental counterpart, endotoxemia, includes a profound dysfunction in myocardial contractility that is resident to the myocyte and associated with reduced systolic free intracellular Ca2+ concentration ([Ca2+]i). We explored the possibility that decreased systolic [Ca2+]iin endotoxemic myocytes is correlated with reduced L-type Ca2+ current ( I Ca,L). Ventricular myocytes were isolated from guinea pigs 4 h after an intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS; 4 mg/kg). Membrane potentials and Ca2+ currents were measured using whole cell patch-clamp methods. The action potential duration of endotoxemic myocytes was significantly shorter than control values (time to 50% repolarization: LPS, 314 ± 23 ms; control, 519 ± 36 ms, P < 0.05). Correspondingly, endotoxemic myocytes demonstrated significantly reduced peak I Ca,L density (3.5 ± 0.2 pA/pF) and Ba2+current ( I Ba) density (7.3 ± 0.5 pA/pF) compared with respective values of control myocytes ( I Ca,L density 6.1 ± 0.3 pA/pF, I Ba density 11.3 ± 0.8 pA/pF; P < 0.05). Endotoxemia-induced reduction in peak I Ca,L could not be attributed to alterations in current-voltage relationships, steady-state activation and inactivation, or recovery from inactivation. The β-adrenoceptor agonist isoproterenol, but not the Ca2+ channel activator BAY K 8644, reversed the LPS-induced reduction in peak I Ca,L, cell contraction, and systolic [Ca2+]i. These data demonstrate that part of the host response to endotoxemia involves diminished sarcolemmal I Ca,L of ventricular myocytes.