Remodeling of Kv4.3 potassium channel gene expression under the control of sex hormones.
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.
Song
M
M
Department of Anesthesiology, School of Medicine, University of California at Los Angeles, California 90095-1778, USA.
Helguera
G
G
Eghbali
M
M
Zhu
N
N
Zarei
M M
MM
Olcese
R
R
Toro
L
L
Stefani
E
E
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D003001:Cloning, Molecular; D017931:DNA Primers; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051672:Shal Potassium Channels; D014599:Uterus / Q000378:metabolism; D014982:Xenopus laevis
D017931:DNA Primers; D012739:Gonadal Steroid Hormones; C497023:Kcnd3 protein, rat; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D012333:RNA, Messenger; D051672:Shal Potassium Channels