Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel.
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.
Philipson
L H
LH
Department of Medicine, University of Chicago, IL 60637.
Hice
R E
RE
Schaefer
K
K
LaMendola
J
J
Bell
G I
GI
Nelson
D J
DJ
Steiner
D F
DF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006801:Humans; D007340:Insulinoma / Q000235:genetics* / Q000503:physiopathology; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009865:Oocytes / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014981:Xenopus
D015345:Oligonucleotide Probes; D015221:Potassium Channels; D012333:RNA, Messenger