title: Elimination of potassium channel expression by antisense oligonucleotides in a pituitary cell line.
abstract: The clonal rat pituitary cell line GH4C1 expresses the genes for several voltage-dependent potassium channels including Kv1.5 and Kv1.4. Dexamethasone, a glucocorticoid agonist, induces a slowly inactivating potassium current in these cells but does not alter the amplitude of a rapidly inactivating component of potassium current. We have found that the induction of the slowly inactivating current can be blocked by an antisense phosphorothioate deoxyoligonucleotide to the Kv1.5 mRNA sequence. In contrast, antisense deoxyoligonucleotides against Kv1.4 mRNA specifically decrease the expression of the dexamethasone-insensitive rapidly inactivating current. These results demonstrate the usefulness of antisense oligonucleotides in correlating potassium currents with specific potassium channel proteins in the cell types in which they are naturally expressed.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: S
authors.initials: S
authors.lastname: Chung
authors.forename: D B
authors.initials: DB
authors.lastname: Saal
authors.forename: L K
authors.initials: LK
authors.lastname: Kaczmarek
mesh_terms: D000818:Animals; D001483:Base Sequence; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002999:Clone Cells; D003907:Dexamethasone / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000096:biosynthesis* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051381:Rats; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013873:Thionucleotides
chemical_list: C496979:Kcna4 protein, rat; C496983:Kcna5 protein, rat; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D016376:Oligonucleotides, Antisense; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D013757:Tetraethylammonium Compounds; D013873:Thionucleotides; D004533:Egtazic Acid; D019789:Tetraethylammonium; D003907:Dexamethasone