ALTERED K-EXPRESSION( CHANNEL SUBUNIT COMPOSITION FOLLOWING HORMONE INDUCTION OF KV1.5 GENE)

Diverse voltage-gated K+ channels are produced by tetramerization of c hannel a subunits that can be encoded by multiple genes. In GH(3) pitu itary cells, the Kv1.4 and Kv1.5 subunit genes are constitutively expr essed, and dexamethasone selectively up-regulates expression of the la tter gene. Here we use subunit-specific antibodies to determine the ef fect of Kv1.5 gene induction on expression of homomeric and heteromeri c channels. In control cells, almost all detectable Kv1.4 proteins are associated with Kv1.5 protein, whereas only similar to 30% Kv1.5 prot ein is present as Kv1.4/Kv1.5 heteromeric channels. Dexamethasone trea tment 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 wit hout affecting Kv1.4 proteins in either fraction. Thus, hormone induct ion of one K+ channel subunit gene differentially influences expressio n of cell surface homomeric and heteromeric channels leading to specif ic alteration of excitability.