Molecular Diversity of K Channels in Cardiovascular System.

早期K^+ （A型）失活电流广泛存在于神经元、心肌细胞和平滑肌细胞中。电流对动作电位放电和动作电位复极相的形成起着重要的调节作用。虽然在心肌细胞和大脑中有几个不同的基因编码负责A型K^+电流（I_A）的K^+通道，但在平滑肌细胞中还没有发现。平滑肌细胞（输精管、结肠和输尿管）中I_A的电生理特征与心肌细胞相似。然而，发现花生四烯酸选择性阻断平滑肌细胞的I_A （Am.J.Physiol.1997）。利用RT-PCR技术检测了平滑肌中I_A的K^+通道基因与心肌细胞中I_A的K^+通道基因不同的可能性。此外，还克隆了大鼠平滑肌细胞中相关的K^+通道。Kv1.4,4.2和4.3被报道为脑和心肌细胞中的K^+通道。根据这些基因mrna的表达水平，我们发现Kv4.3在平滑肌细胞中占主导地位。此外，平滑肌细胞中的Kv4.3是脑原Kv4.3 （Kv.4.3M）的新剪接变体，在靠近C端的胞质结构域（Kv4.3 l）增加了19个氨基酸（FEBS Letters, 1997）。在大鼠心脏中，Kv4.3L mRNA水平高于Kv4.3M。检测了Kv1.4、4.2、4.3M和4.3L K^+通道在高表达的HEK 293细胞中的电生理特性。Kv4.3L的激活和失活的电压依赖性、失活后的恢复时间以及对花生四烯酸的敏感性与Kv4.3M无显著差异。另外19种氨基酸在Kv4.3L中的功能作用有待进一步研究。我们还发现，编码大电导Ca^<2+>依赖性K^+通道和电压依赖性Ca^<2+>通道的mrna在不同类型平滑肌细胞中的不同表达水平，至少部分解释了不同类型平滑肌细胞膜兴奋性的差异。少

Early inactivating K^+ (A type) current can be recorded widely in neuron, cardiac myocytes and smooth muscle cells. the current plays significant roles for the regulation of action potential firing and formation of the repolarizing phase of an action potential. Although several distinct genes encoding the K^+ channels responsible for A type K^+ current (I_A) in cardiac myocytes and brain have been reported, nothing is known in smooth muscle cells. The electrophysiological characteristics of I_A in smooth muscle cells (vas deferens, colon and ureter) and similar to those in cardiac myocytes. Nevertheless, it was found that arachidonic acid selectively blocks the I_A in smooth muscle cells (Am.J.Physiol.1997). The possibility that the K^+ channel gene for I_A in smooth muscle is deferent from that in cardiac myocytes was examined using RT-PCR techniques. In addition, the related K^+ channels in smooth muscle cells in the rat was cloned. Kv1.4,4.2 and 4.3 have been reported as K^+ channel … More genes in brain and cardiac myocytes. Based on the expression levels of mRNAs of these genes, it was found taht Kv4.3 is predominant among them in smooth muscle cells. Moreover, Kv4.3 in smooth muscle cells was a new spliced variant of the original Kv4.3 (Kv.4.3M) in brain and has additional 19 amino acids in cytosolic domain close to the C terminus (Kv4.3L) (FEBS Letters, 1997). In the rat heart, the mRNA level of Kv4.3L was higher than that of Kv4.3M.Electrophysiological characteristics of Kv1.4,4.2,4.3M and 4.3L K^+ channels were determined in HEK 293 cells in which one of these channel types was highly expressed. The voltage-dependence of activation and inactivation, the recovery time course from inactivation and the sensitivity to arachidonic acid of Kv4.3L were not significantly different from those of Kv4.3M.Further research is required to elucidate the functional roles of additional 19 amino acids in Kv4.3L.It was also found that the different expression levels of mRNAs encoding the large conductance Ca^<2+> -dependent K^+ channels and the voltage-dependent Ca^<2+> channels in various type of smooth muscle cells, at least in part, explains the difference in membrane excitability in different types of smooth muscle cells. Less