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(Received for publication, July 7,
1994; and in revised form, December 21, 1994) Voltage-gated K
Volume 270,
Number 11,
Issue of March 17, 1995 pp. 6036-6041
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Channel
Gene Transcription and Protein Expression in Pituitary Cells
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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