Remodeling of Kv4.3 potassium channel gene expression under the control ofsex hormones

Kv4.3 channels are important molecular components of transient K+ currents (Ito currents) in brain and heart. They are involved in setting the frequen cy of neuronal firing and heart pacing. Altered Kv4.3 channel expression ha s been demonstrated under pathological conditions like heart failure indica ting 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 investigate d whether its expression changes in the pregnant uterus. This organ represe nts a unique model to study Ito currents, because it possesses this type of K+ current and undergoes dramatic changes in function and excitability dur ing pregnancy. We cloned Kv4.3 channel from myometrium and found that its p rotein and transcript expression is greatly diminished during pregnancy. Ex periments in ovariectomized rats demonstrate that estrogen is one mechanism responsible for the dramatic reduction in Kv4.3 expression and function pr ior to parturition. Furthermore, the reduction of plasma membrane Kv4.3 pro tein is accompanied by a perinuclear localization suggesting that cell traf ficking is also controlled by sex hormones. Thus, estrogen remodels the exp ression of Kv4.3 in myometrium by directly diminishing its transcription an d, indirectly, by altering Kv4.3 delivery to the plasma membrane.