Hormonal regulation of potassium currents in single myometrial cells.

Toro, Ligia; Stefani, Enrico; Erulkar, S. D.

doi:10.1073/pnas.87.8.2892

Cited by 43 publications

(35 citation statements)

References 20 publications

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“…The rapidly inactivating 4-AP-sensitive K ϩ current is prominent in myometrial cells (11,19,22,25,30,31) and plays an important role in controlling membrane potential during gestation (19,25). The kinetics and pharmacological properties of this current resemble those produced by channel subunits in the Kv4 family.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy

Suzuki

Takimoto

2005

American Journal of Physiology-Endocrinology and Metabolism

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Regulation of voltage-gated K ϩ (Kv) channel expression may be involved in controlling contractility of uterine smooth muscle cells during pregnancy. Functional expression of these channels is not only controlled by the levels of pore-forming subunits, but requires their association with auxiliary subunits. Specifically, rapidly inactivating Kv current is prominent in myometrial cells and may be carried by complexes consisting of Kv4 pore-forming and KChIP auxiliary subunits. To determine the molecular identity of the channel complexes and their changes during pregnancy, we examined the expression and localization of these subunits in rat uterus. RT-PCR analysis revealed that rat uterus expressed all three Kv4 pore-forming subunits and KChIP2 and -4 auxiliary subunits. The expression of mRNAs for these subunits was dynamically and region selectively regulated during pregnancy. In the corpus, Kv4.2 mRNA level increased before parturition, whereas the expression of Kv4.1 and Kv4.3 mRNAs decreased during pregnancy. A marked increase in KChIP2 mRNA level was also seen at late gestation. In the cervix, the expression of all three pore-forming and two auxiliary subunit mRNAs increased at late gestation. Immunoprecipitaton followed by immunoblot analysis indicated that Kv4.2-KChIP2 complexes were significant in uterus at late pregnancy. Kv4.2-and KChIP2-immunoreactive proteins were present in both circular and longitudinal myometrial cells. Finally, Kv4.2 and KChIP2 mRNA levels were similarly elevated in pregnant and nonpregnant corpora of one side-conceived rats. These results suggest that diffusible factors coordinate the pregnancy-associated changes in molecular compositions of myometrial Kv4-KChIP channel complexes.

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Section: Discussionmentioning

confidence: 99%

Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy

Suzuki

Takimoto

2005

American Journal of Physiology-Endocrinology and Metabolism

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“…Effect of glibenclamide on 86Rb efflux and contractions in cyanide A variety of K+ channels have been described in the uterus (Toro, Stefani & Erulkar 1990) (Standen, Quayle, Davies, Brayden, Huang & Nelson, 1989;Piper, Minshall, Downing, Hollingsworth & Sadraei, 1990). The effects of glibenclamide (20 #M) on the rate constant of 86Rb efflux in cyanide were therefore examined.…”

Section: Resultsmentioning

confidence: 99%

“…Thus although gestational conditions may alter K+ channel conductances in the uterus (Toro et al 1990), such changes were not influencing the response to cyanide. The greater depression of contraction by cyanide in nonpregnant compared to pregnant uteri must reside in some other effect of cyanide; for example, the greater fall in [ATP] and [PCr] (Wray, 1990).…”

Section: Discussionmentioning

confidence: 99%

Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.

Heaton

Wray

Eisner

1993

The Journal of Physiology

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SUMMARY1. We have investigated the role of changes of potassium efflux in the inhibition of uterine force produced by cyanide. K+ efflux (86Rb) was measured from pregnant and non-pregnant rat myometrial strips during metabolic inhibition with cyanide and following manoeuvres to displace intracellular pH (pHi).2. Cyanide greatly reduced or abolished spontaneous contractions. If the membrane was depolarized directly at this stage (by elevating external K+) then contraction redeveloped. This suggests that the initial depression of force is due to a failure of membrane excitation.3. Cyanide reversibly increased 86Rb efflux (30-35%) in both pregnant and nonpregnant uteri and contraction was reduced. The increase in 86Rb efflux with cyanide was not secondary to changes of membrane potential as it also occurred in both high-K+ and Ca2+-free solutions. 6. Intracellular alkalinization produced by the weak base trimethylamine (60 mM) increased the frequency of uterine contraction and the 86Rb efflux. However, there was no effect on the 86Rb efflux in a Ca2+-free solution. The increased efflux is therefore presumably a consequence of the increased frequency.7. It is concluded that metabolic inhibition produced by cyanide, produces an increase in K+ efflux from the myometrium. Part of this efflux is glibenclamide sensitive. This increased K+ efflux will lead to hyperpolarization of the myometrial membrane and thus decrease excitation. Thus reduced surface membrane excitability will contribute to the fall of force in hypoxia; specifically it may cause the initial loss of spontaneous contractions in the uterus.MS 1322

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“…While the physiological role of minK channels in heart and epithelial cells becomes apparent (Busch et al 1994;Wangemann et al 1995;Suessbrich et al 1996), their role in the uterus remains unclear. The excitability of uterus during pregnancy is controlled by the estrogen blood concentration which influences the expression of a number of distinct ion channels (for review see Parkington and Coleman 1988;Toro et al 1990). For rat uterus it was shown that minK RNA is dramatically increased at high estrogen blood concentrations (Folander et al 1990), and a role for minK in labour induction has been proposed (Boyle et al 1987).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of minK protein induced K+ channels in Xenopus oocytes by estrogens

Waldegger

Lang

Herzer

et al. 1996

Naunyn-Schmiedeberg's Arch Pharmacol

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Previously it was shown that minK protein expression in uterus is regulated by estrogen. In the present study, we were interested in putative direct effects of estrogen on minK protein induced K+ currents (IminK) in Xenopus oocytes. Superfusion with 17-beta-estradiol (1 microM) resulted in an inhibition of minK-induced currents, but had no appreciable effects on the delayed rectifier and inward rectifier K+ channels Kv1.1 and Kir2.1, respectively. The inhibition of IminK by 17-beta-estradiol was concentration-dependent, with an IC50 of approximately 0.5 microM. In the presence of 17-beta-estradiol, the conductance-voltage relationship was shifted to more depolarized potentials. IminK inhibition occurred also in the presence of the estrogen-receptor antagonist tamoxifen, suggesting that a mechanism independent of estrogen receptors is involved. The synthetic estrogen diethylstilbestrol (DES) also inhibited IminK but with a lower affinity (IC50 of 4.5 microM), while cortisol and progesterone had only weak effects on IminK. In summary, the results indicate that estrogens directly inhibit IminK.

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Hormonal regulation of potassium currents in single myometrial cells.

Cited by 43 publications

References 20 publications

Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy

Differential expression of Kv4 pore-forming and KChIP auxiliary subunits in rat uterus during pregnancy

Effects of metabolic inhibition and changes of intracellular pH on potassium permeability and contraction of rat uterus.

Inhibition of minK protein induced K+ channels in Xenopus oocytes by estrogens

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