Altered K+ channel subunit composition following hormone induction of Kv1.5 gene expression.
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.
Department of Pharmacology, University of Pittsburgh, Pennsylvania 15261, USA.
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Takimoto
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Levitan
D000818:Animals; D016466:CHO Cells; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D046911:Macromolecular Substances; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011233:Precipitin Tests; D051381:Rats; D011994:Recombinant Proteins
D005938:Glucocorticoids; C496979:Kcna4 protein, rat; C496983:Kcna5 protein, rat; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D046911:Macromolecular Substances; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011994:Recombinant Proteins; D003907:Dexamethasone