The adenosine 5'-triphosphate-sensitive potassium channel in endocrine cells of the human ovary: role in membrane potential generation and steroidogenesis.
BACKGROUND
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.


METHODS
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(ir)6.1, but not K(ir)6.2, as indicated by RT-PCR. K(ir)6.1 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(ir)6.1 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.
Anatomical Institute, University of Munich, Biedersteiner Str. 29, D-80802 Munich, Germany. lars.kunz@lrz.uni-muenchen.de
Lars
L
Kunz
Johanna S
JS
Richter
Artur
A
Mayerhofer
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D054086:KATP Channels; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000502:physiology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis*; D013347:Subcellular Fractions / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; D054086:KATP Channels; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D013256:Steroids; C092520:uK-ATP-1 potassium channel; D011374:Progesterone