Takimoto K, Levitan E S
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.
Biochemistry. 1996 Nov 12;35(45):14149-56. doi: 10.1021/bi961290s.
Diverse voltage-gated K+ channels are produced by tetramerization of channel alpha subunits that can be encoded by multiple genes. In GH3 pituitary cells, the Kv1.4 and Kv1.5 subunit genes are constitutively expressed, and dexamethasone selectively up-regulates expression of the latter gene. Here we use subunit-specific antibodies to determine the effect of Kv1.5 gene induction on expression of homomeric and heteromeric channels. In control cells, almost all detectable Kv1.4 proteins are associated with Kv1.5 protein, whereas only approximately 30% Kv1.5 protein is present as Kv1.4/Kv1.5 heteromeric channels. Dexamethasone treatment doubled expression of Kv1.5 homomeric channels but only modestly up-regulated Kv1.4/Kv1.5 heteromeric complexes. The steroid treatment similarly increased total cellular and cell surface Kv1.5 protein without affecting Kv1.4 proteins in either fraction. Thus, hormone induction of one K+ channel subunit gene differentially influences expression of cell surface homomeric and heteromeric channels leading to specific alteration of excitability.
多种电压门控性钾离子通道由通道α亚基四聚化产生，这些亚基可由多个基因编码。在GH3垂体细胞中，Kv1.4和Kv1.5亚基基因组成性表达，地塞米松可选择性上调后一个基因的表达。在此，我们使用亚基特异性抗体来确定Kv1.5基因诱导对同型和异型通道表达的影响。在对照细胞中，几乎所有可检测到的Kv1.4蛋白都与Kv1.5蛋白相关，而只有约30%的Kv1.5蛋白以Kv1.4/Kv1.5异型通道的形式存在。地塞米松处理使Kv1.5同型通道的表达增加了一倍，但仅适度上调了Kv1.4/Kv1.5异型复合物。类固醇处理同样增加了总细胞和细胞表面的Kv1.5蛋白，而不影响任何一个组分中的Kv1.4蛋白。因此，一个钾离子通道亚基基因的激素诱导对细胞表面同型和异型通道的表达有不同影响，导致兴奋性发生特定改变。
