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J. Biol. Chem., Vol. 276, Issue 34, 31883-31890, August 24, 2001
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From the Departments of Kv4.3 channels are important molecular components
of transient K+ currents (Ito currents) in brain and
heart. They are involved in setting the frequency of neuronal firing
and heart pacing. Altered Kv4.3 channel expression has been
demonstrated under pathological conditions like heart failure
indicating their critical role in heart function. Thyroid hormone
studies suggest that their expression in the heart may be hormonally
regulated. To explore the possibility that sex hormones control Kv4.3
expression, we investigated whether its expression changes in the
pregnant uterus. This organ represents a unique model to study Ito
currents, because it possesses this type of K+ current and
undergoes dramatic changes in function and excitability during
pregnancy. We cloned Kv4.3 channel from myometrium and found that its protein and transcript expression is greatly diminished during pregnancy. Experiments in ovariectomized rats demonstrate that
estrogen is one mechanism responsible for the dramatic reduction in
Kv4.3 expression and function prior to parturition. Furthermore, the
reduction of plasma membrane Kv4.3 protein is accompanied by a
perinuclear localization suggesting that cell trafficking is also
controlled by sex hormones. Thus, estrogen remodels the expression of
Kv4.3 in myometrium by directly diminishing its transcription and,
indirectly, by altering Kv4.3 delivery to the plasma membrane.
Remodeling of Kv4.3 Potassium Channel Gene Expression
under the Control of Sex Hormones*
§,§,§,,,,¶
**, and§§
Anesthesiology,
Physiology, and ¶ Molecular & Medical
Pharmacology and Brain Research Institute, School of Medicine,
University of California at Los Angeles, California 90095-1778
*
This work was supported in part by National Institutes of
Health Grants GM52203 (to E. S.) and HL54970 (to L. T.) and by Human Frontier Research Program Organization (to L. T.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) AF334791.
§§ To whom correspondence should be addressed: Dept. of Anesthesiology, UCLA School of Medicine, BH-509A CHS, Box 957115, Los Angeles, CA 90095-7115. Tel.: 310-794-7808; Fax: 310-825-6649; E-mail: estefani@ucla.edu.Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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