The Adenosine 5′-Triphosphate-Sensitive Potassium Channel in Endocrine Cells of the Human Ovary: Role in Membrane Potential Generation and Steroidogenesis

Context: ATP-sensitive potassium (K_ATP) channels couple the metabolic state with the membrane potential in several cell types, and recently evidence for K_ATP channels was given in rat corpus luteum, a fast-growing and metabolically highly active tissue.

Objective: We studied whether K_ATP channels are present in the human ovary and luteinized granulosa cells (GCs). Human GCs were examined regarding functionality and physiological role of the channel.

Patients and Intervention: Human GCs were obtained from in vitro fertilization patients.

Results: K_ATP channels are involved in membrane potential generation in human GCs because application of the K_ATP blocker glibenclamide resulted in depolarization as monitored by fluorescence microscopy. Furthermore, glibenclamide significantly attenuated human chorionic gonadotropin-induced progesterone production. The channel pore is composed of K_ir6.1, but not K_ir6.2, as indicated by RT-PCR. K_ir6.1 subunit protein was detected in human follicular and luteal cells by immunohistochemistry and localized to the plasma membrane of human GCs by immunogold staining. RT-PCR experiments revealed the sulfonylurea receptor subunit SUR2B as part of the K_ATP channel. In addition, mRNAs encoding SUR1 and SUR2A were detected in some preparations. There is no evidence for mitochondrial K_ATP channels in human GCs because we detected neither K_ir6.1 protein in mitochondrial membranes nor alterations of mitochondrial membrane potential by glibenclamide or the K_ATP opener diazoxide.

Conclusions: Endocrine cells of the human ovary possess functional K_ATP channels, which are linked to both plasma membrane potential generation and progesterone production. Our results may provide new insights into human ovarian physiology and raise the possibility of pharmacological targeting.