Membrane depolarization inhibits Kv1.5 voltage-gated K+ channel gene transcription and protein expression in pituitary cells

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

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

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 Ca2+ 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 Ca2+-independent inhibition of Kv1.5 gene transcription may produce a long-term enhancement of pituitary cell excitability and secretory activity.

Original languageEnglish (US)
Pages (from-to)6036-6041
Number of pages6
JournalJournal of Biological Chemistry
Volume270
Issue number11
DOIs
StatePublished - Mar 17 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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