Obstet Gynecol Sci.  2020 Sep;63(5):565-576. 10.5468/ogs.20064.

Role of potassium channels in female reproductive system

• Kim JM
• Song KS
• Xu B
• Wang T

• KMID: 2506499
• DOI: http://doi.org/10.5468/ogs.20064

Abstract

Potassium channels are widely expressed in most types of cells in living organisms and regulate the functions of a variety of organs, including kidneys, neurons, cardiovascular organs, and pancreas among others. However, the functional roles of potassium channels in the reproductive system is less understood. This mini-review provides information about the localization and functions of potassium channels in the female reproductive system. Five types of potassium channels, which include inward-rectifying (Kir), voltage-gated (Kv), calcium-activated (KCa), 2-pore domain (K2P), and rapidly-gating sodium-activated (Slo) potassium channels are expressed in the hypothalamus, ovaries, and uterus. Their functions include the regulation of hormone release and feedback by Kir6.1 and Kir6.2, which are expressed in the luteal granulosa cells and gonadotropin-releasing hormone neurons respectively, and regulate the functioning of the hypothalamus–pituitary–ovarian axis and the production of progesterone. Both channels are regulated by subtypes of the sulfonylurea receptor (SUR), Kir6.1/SUR2B and Kir6.2/SUR1. Kv and Slo2.1 affect the transition from uterine quiescence in late pregnancy to the state of strong myometrial contractions in labor. Intermediate- and small-conductance KCa modulate the vasodilatation of the placental chorionic plate resistance arteries via the secretion of nitric oxide and endothelium-derived hyperpolarizing factors. Treatment with specific channel activators and inhibitors provides information relevant for clinical use that could help alter the functions of the female reproductive system.

Keyword

Potassium channels; Gonadal steroid hormones; Ovary; Uterus; Placenta

Figure

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  Fig. 1. The amounts of potassium of daily dietary intake, distribution in intracellular fluid (ICF) and extracelluler fluid (ECF), and daily fecal and urinary excretion. Most dietary potassium is excreted by the kidney (up to 80 mEq/day intake vs. up to 72 mEq/day in the urine) to maintain normal potassium concentrations. Approximately 98% of potassium is present in the ICF (up to 3,300 mEq), while the other 2% present in the extracellular compartment (up to 70 mEq) which is usually maintained within a narrow range (3.8–4.5 mEq/L) in serum. Hypokalemia has many causes including: excessive potassium loss due to diarrhea, excessive sweating from exercise, abuse of alcohol, some diuretics, or laxatives. In contrast, hyperkalemia can be occurred due to acute kidney failure, chronic kidney disease, medication such as angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, or beta blockers, and dehydration or excessive potassium supplements.

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  Fig. 2. Involvement potassium channels in hypothallus-pituitary-ovarian axis. While progesterone secretion is mediated by the Kir6.1/SUR2B, KATP channels subtype in the ovary, Kir6.2/SUR1 subunits is predominantly expressed in gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus. The KATP channel Kir6.2/SUR1 modulates the pulsatile release of GnRH, and activity of the KATP channels responds to negative feedback from ovarian steroids-E2 and progesterone. The acetylcholine and oxytocin increase intracellular Ca2+ concentration in lutein-granulosa cells, the intracellular calcium signal affects progesterone release via BKCa. human chorionic gonadotropin stimulates the release of oxytocin, which, along with acetylcholine, acts as an ovarian signaling molecule. LH, luteinizing hormone.

Reference

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