Leicher T, Roeper J, Weber K, Wang X, Pongs O
Zentrum für Molekulare Neurobiologie, Institut für Neurale Signalverarbeitung, Hamburg, Germany.
Neuropharmacology. 1996;35(7):787-95. doi: 10.1016/0028-3908(96)00133-5.
Voltage-activated Shaker-related potassium channels (kv1) consist of alpha and beta subunits. We have analysed the structure of the human KCNA1B (hKv beta 1) gene. KCNA1B is > 250 kb in size and encodes at least three Kv beta 1 splice variants. The Kv beta 1 open reading frame is divided into 14 exons. In contrast, genes coding for family members of KCNA (Kv 1 alpha) subunits are markedly smaller and have intronless open reading frames. The expression of Kv 1 alpha and Kv beta mRNA was compared in Northern blots of poly(A+) RNA isolated from various human brain tissues. The results suggest an intricate and cell-specific regulation of Kv 1 alpha and Kv beta mRNA synthesis such that distinct combinations of alpha and beta subunits would occur in different nuclei of the brain. The splice variants hKv beta 1.1 and hKv beta 1.2 were functionally characterized in coexpression studies with hKv 1.5 alpha subunits in 293 cells. It is shown that the confer rapid inactivation on hKv 1.5 channels with different potencies. This may be due to differences in their amino terminal sequences and/or inactivating domains. It is also shown that the amino terminal Kv beta 1.1 and Kv 1.4 alpha inactivating domains compete with each other, probably for the binding to the same receptor site(s) on Kv 1 alpha-subunits.
电压激活的与Shaker相关的钾通道（kv1）由α和β亚基组成。我们分析了人类KCNA1B（hKvβ1）基因的结构。KCNA1B大小超过250 kb，编码至少三种Kvβ1剪接变体。Kvβ1开放阅读框被分为14个外显子。相比之下，编码KCNA（Kv 1α）亚基家族成员的基因明显更小，且有无内含子的开放阅读框。在从各种人类脑组织中分离的聚腺苷酸（A+）RNA的Northern印迹中比较了Kv 1α和KvβmRNA的表达。结果表明Kv 1α和KvβmRNA合成存在复杂的细胞特异性调控，使得α和β亚基的不同组合会出现在大脑的不同核团中。在293细胞中与hKv 1.5α亚基进行共表达研究，对剪接变体hKvβ1.1和hKvβ1.2进行了功能表征。结果表明它们以不同效力使hKv 1.5通道快速失活。这可能是由于它们氨基末端序列和/或失活结构域的差异。还表明氨基末端的Kvβ1.1和Kv 1.4α失活结构域相互竞争，可能是为了与Kv 1α亚基上的相同受体位点结合。
