Different intracellular polyamine concentrations underlie the difference in the inward rectifier K+ currents in atria and ventricles of the guinea‐pig heart
Different intracellular polyamine concentrations underlie the difference in the inward rectifier K+ currents in atria and ventricles of the guinea‐pig heart
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DOI：
10.1113/jphysiol.2004.077677
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发表时间：
2005-03
期刊：
影响因子：
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通讯作者：
Ding-Hong Yan;K. Nishimura;Kaori Yoshida;K. Nakahira;T. Ehara;K. Igarashi;K. Ishihara
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文献类型：
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作者：
Ding-Hong Yan;K. Nishimura;Kaori Yoshida;K. Nakahira;T. Ehara;K. Igarashi;K. Ishihara
强内向整流钾电流IK1在心室的外向分量明显大于心房，导致心室动作电位末相的复极化更快。然而，IK1差异的潜在机制仍然知之甚少。IK1通道由Kir2亚家族的亚基组成，IK1的振幅由细胞内多胺精胺和亚精胺以及Mg2+对通道的电压依赖性阻断决定。使用穿孔膜片钳法，可以最大限度地减少细胞内多胺和Mg2+浓度的变化，我们在豚鼠心脏的心室肌细胞而不是心房肌细胞中检测到复极化诱导的外向IK1瞬变，这是由Mg2+和精胺之间的竞争来阻断通道引起的。在豚鼠心脏中，Kir2.3亚基对IK1通道的贡献很小，因为Kir2.3电流的激活时间过程比IK1慢约10倍，而且在IK1中没有发现Kir2.3电流明显的外部pH敏感性。在5 ~ 10 μm精胺和0.6 ~ 1.1 mm Mg2+存在的情况下，Kir2.1和Kir2.2电流均表现出与心室IK1相似的向外瞬变，且其振幅随精胺或亚精胺浓度的增加而减弱。豚鼠心脏组织中总多胺和游离多胺浓度在心房高于心室。这些结果强烈表明，不同的细胞内多胺浓度是导致豚鼠心脏心房和心室IK1差异的原因。
The outward component of the strong inward rectifier potassium current, IK1, is significantly larger in ventricles than in atria of the heart, resulting in faster repolarization at the final phase of the action potential in ventricles. However, the underlying mechanism of the difference in IK1 remains poorly understood. IK1 channels are composed of subunits from the Kir2 subfamily, and IK1 amplitude is determined by the voltage‐dependent blockade of the channel by the intracellular polyamines spermine and spermidine, and by Mg2+. Using a perforated patch‐clamp method, which minimizes changes in the intracellular polyamine and Mg2+ concentrations, we detected repolarization‐induced outward IK1 transients, which are caused by competition between Mg2+ and spermine to block the channel, in ventricular but not in atrial myocytes from guinea‐pig heart. The contribution of the Kir2.3 subunit to the IK1 channel was found to be minor in the guinea‐pig heart, because the activation time course of the Kir2.3 currents was ∼10‐fold slower than those of IK1, and the marked external pH sensitivity of the Kir2.3 currents was not found in IK1. Both the Kir2.1 and Kir2.2 currents recorded from inside‐out patches exhibited outward transients similar to those of ventricular IK1 in the presence of 5–10 μm spermine and 0.6–1.1 mm Mg2+, and their amplitudes were diminished by increasing the spermine or spermidine concentrations. The total and free polyamine concentrations in guinea‐pig cardiac tissues were higher in atria than ventricles. These results strongly suggest that different intracellular polyamine concentrations are responsible for the difference in atrial and ventricular IK1 of the guinea‐pig heart.