Philipson L H, Hice R E, Schaefer K, LaMendola J, Bell G I, Nelson D J, Steiner D F
Department of Medicine, University of Chicago, IL 60637.
Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):53-7. doi: 10.1073/pnas.88.1.53.
Regulation of insulin secretion involves the coordinated control of ion channels in the beta-cell membrane. We have isolated and characterized cDNA and genomic clones encoding a voltage-dependent K+ channel isoform expressed in human islets and in a human insulinoma. This K+ channel isoform, designated hPCN1, with a deduced amino acid sequence of 613 residues (Mr = 67,097), is related to the Shaker family of Drosophila K+ channels. hPCN1 is homologous to two other human K+ channel isoforms we have isolated, hPCN2 and hPCN3, with 55% and 65% amino acid sequence identity, respectively. The electrophysiological characteristics of hPCN1 were determined after microinjection of synthetic RNA into Xenopus oocytes. Two-microelectrode voltage-clamp recordings of oocytes injected with hPCN1 RNA revealed a voltage-dependent outward K+ current that inactivated slowly with time. Outward currents were inhibited by 4-aminopyridine with a Ki less than 0.10 mM and were relatively insensitive to tetraethylammonium ion or Ba2+. A delayed rectifier K+ channel such as hPCN1 could restore the resting membrane potential of beta cells after depolarization and thereby contribute to the regulation of insulin secretion.
胰岛素分泌的调节涉及β细胞膜中离子通道的协同控制。我们已经分离并鉴定了编码在人胰岛和人胰岛素瘤中表达的电压依赖性钾离子通道亚型的cDNA和基因组克隆。这种钾离子通道亚型，命名为hPCN1，推导的氨基酸序列有613个残基（Mr = 67,097），与果蝇钾离子通道的Shaker家族相关。hPCN1与我们分离的另外两种人钾离子通道亚型hPCN2和hPCN3同源，氨基酸序列同一性分别为55%和65%。将合成RNA显微注射到非洲爪蟾卵母细胞后，测定了hPCN1的电生理特性。对注射了hPCN1 RNA的卵母细胞进行双微电极电压钳记录，显示出一种电压依赖性外向钾离子电流，该电流随时间缓慢失活。外向电流被4-氨基吡啶抑制，Ki小于0.10 mM，并且对四乙铵离子或Ba2+相对不敏感。像hPCN1这样的延迟整流钾离子通道可以在去极化后恢复β细胞的静息膜电位，从而有助于胰岛素分泌的调节。
