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

59 Citations (Scopus)

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

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Voltage-Gated Potassium Channels
Depolarization
Transcription
Genes
Membranes
Messenger RNA
Proteins
Down-Regulation
Endocrine Cells
Muscle Cells
Action Potentials
Neurons
Muscle
Cells
Peptides
Antibodies

ASJC Scopus subject areas

  • Biochemistry

Cite this

Membrane depolarization inhibits Kv1.5 voltage-gated K+ channel gene transcription and protein expression in pituitary cells. / Levitan, Edwin S.; Gealy, Robert; Trimmer, James; Takimoto, Koichi.

In: Journal of Biological Chemistry, Vol. 270, No. 11, 17.03.1995, p. 6036-6041.

Research output: Contribution to journalArticle

Levitan, Edwin S. ; Gealy, Robert ; Trimmer, James ; Takimoto, Koichi. / Membrane depolarization inhibits Kv1.5 voltage-gated K+ channel gene transcription and protein expression in pituitary cells. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 11. pp. 6036-6041.
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