Na+/Ca2+ exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart
Na+/Ca2+ exchanger inhibition exerts a positive inotropic effect in the rat heart, but fails to influence the contractility of the rabbit heart
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DOI：
10.1038/bjp.2008.83
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发表时间：
2008-05-01
影响因子：
7.3
通讯作者：
Farkas, A.
中科院分区：
文献类型：
--
作者：
Farkas, A. S.;Acsai, K.;Farkas, A.
背景与目的：Na+/Ca ~（2+）交换体（NCX）可能在心肌收缩性中起关键作用。NCX的运作受动作电位（AP）构型和细胞内Na+浓度的影响。本研究探讨了选择性NCX抑制0.1，0.3和1.0 μ M的SEA 0400在不同AP配置和不同的细胞内Na+浓度在兔和大鼠hearts.Experimental方法的设置对心肌收缩力的影响：SEA 0400对I-Na/Ca的浓度依赖性影响进行了研究，在大鼠和兔心室心肌细胞使用膜片钳技术。建立离体Langendorff灌注大鼠和兔心脏的Starling曲线。两个物种的心脏肌膜NCX蛋白密度进行了比较通过immunohistochemistry.Key results：SEA 0400抑制INa/Ca在两个物种中具有相似的功效;在两个物种中NCX的正向或反向模式的抑制之间没有差异。SEA 0400以浓度依赖性方式增加大鼠心脏的收缩压和发展压，例如，1.0 mM SEA 0400相对于对照增加最大收缩压12%，而它不能改变兔心脏的收缩性。没有种间差异被发现在心脏肌膜NCX蛋白density.Conclusions和影响：NCX抑制产生了积极的变力作用，在大鼠心脏，但它不影响兔心脏的收缩性。这意味着AP构型和细胞内Na+浓度可能在NCX抑制的收缩反应中起重要作用。
Background and purpose: The Na+/Ca2+ exchanger (NCX) may play a key role in myocardial contractility. The operation of the NCX is affected by the action potential (AP) configuration and the intracellular Na+ concentration. This study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 mu M SEA0400 on the myocardial contractility in the setting of different AP configurations and different intracellular Na+ concentrations in rabbit and rat hearts.Experimental approach: The concentration-dependent effects of SEA0400 on I-Na/Ca were studied in rat and rabbit ventricular cardiomyocytes using a patch clamp technique. Starling curves were constructed for isolated, Langendorff-perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of both species were compared by immunohistochemistry.Key results: SEA0400 inhibited INa/Ca with similar efficacy in the two species; there was no difference between the inhibitions of the forward or reverse mode of the NCX in either species. SEA0400 increased the systolic and the developed pressure in the rat heart in a concentration-dependent manner, for example, 1.0 mM SEA0400 increased the maximum systolic pressures by 12% relative to the control, whereas it failed to alter the contractility in the rabbit heart. No interspecies difference was found in the cardiac sarcolemmal NCX protein densities.Conclusions and implications: NCX inhibition exerted a positive inotropic effect in the rat heart, but it did not influence the contractility of the rabbit heart. This implies that the AP configuration and the intracellular Na+ concentration may play an important role in the contractility response to NCX inhibition.