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Volume 270, Number 11, Issue of March 17, 1995 pp. 6036-6041
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Membrane Depolarization Inhibits Kv1.5 Voltage-gated K Channel Gene Transcription and Protein Expression in Pituitary Cells

(Received for publication, July 7, 1994; and in revised form, December 21, 1994)

Edwin S. Levitan Robert Gealy James S. Trimmer Koichi Takimoto

Voltage-gated K channels play an essential role in the production of action potential activity by excitable cells. Recent studies have suggested that expression of K channel genes may be regulated by stimuli that affect electrical activity. Elevating the concentration of extracellular KCl causes membrane depolarization and, thus, is widely used for studying electrical activity-dependent changes in neurons, muscle, and endocrine cells. Here we show that elevated KCl decreases Kv1.5 K channel mRNA expression in clonal pituitary cells without affecting Kv1.4 and Kv2.1 mRNA levels. K channel blockers, which cause depolarization, also produce down-regulation of Kv1.5 mRNA, while NaCl addition had no effect. Thus, the effect of KCl is mediated by K-induced membrane depolarization. Unlike many known effects of K, down-regulation of Kv1.5 mRNA does not require Ca or Na influx, or Na-H exchange. Furthermore, the decrease in Kv1.5 mRNA expression is due to inhibition of channel gene transcription and persists after inhibition of protein synthesis, excluding a role for induction of intermediary regulatory proteins. Finally, immunoblots with antibody specific for the Kv1.5 polypeptide show that depolarization for 8 h reduces the expression of Kv1.5 channel protein. The decrease in K channel protein expression caused by depolarization-induced Ca-independent inhibition of Kv1.5 gene transcription may produce a long-term enhancement of pituitary cell excitability and secretory activity.




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